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PURPOSE OF REVIEW: Female periurethral masses are an uncommon occurrence. The purpose of this review is to describe etiologies of female urethral and periurethral masses and to provide an update on diagnosis and management. RECENT FINDINGS: The most common causes of periurethral and urethral masses in women are urethral caruncles, urethral diverticula, and Skene's gland cysts. Urethral meatal lesions such as urethral caruncles and prolapse can be managed conservatively with topical estrogen therapy and close follow-up or should be excised in the setting of thrombosis, significant or recurrent bleeding, acute urinary retention, or persistent pain. Benign periurethral gland masses, such as Skene's gland cysts, Gartner's duct cysts, and Mullerian duct cysts, remain rare. Recent case series reveal a high rate of surgical management of these lesions with few complications. Urethral malignancy or malignant transformation of benign etiologies are even rarer but can be aggressive in nature and should be treated promptly. SUMMARY: Nonspecific urinary and vaginal symptoms as well as similar physical presentations make diagnosis of urethral and periurethral lesions in females difficult. Magnetic resonance imaging is useful for differentiation of periurethral masses. The decision for conservative or surgical management is typically guided by patient symptom bother, as well as concern for urethral malignancy.
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Cistos , Doenças Uretrais , Neoplasias Uretrais , Feminino , Humanos , Neoplasias Uretrais/diagnóstico , Neoplasias Uretrais/terapia , Uretra/cirurgia , Doenças Uretrais/diagnóstico , Doenças Uretrais/cirurgia , Imageamento por Ressonância Magnética/métodos , Cistos/diagnóstico , Cistos/cirurgiaRESUMO
INTRODUCTION AND HYPOTHESIS: Factors that contribute to reoperation and surgical approaches for the management of recurrent uterovaginal prolapse after vaginal mesh hysteropexy (mesh hysteropexy) are unknown. We aimed to describe surgical management of pelvic organ prolapse recurrence after vaginal mesh hysteropexy, and patient characteristics in those who chose reoperation. METHODS: This is a descriptive analysis of women who experienced treatment failure within 5 years of mesh hysteropexy in a multi-site randomized trial. The composite definition of treatment failure included retreatment (pessary or reoperation), prolapse beyond the hymen, or bothersome prolapse symptoms. Characteristics of those pursuing and not pursuing repeat prolapse surgery, measures of prolapse, and symptom severity are described. RESULTS: Over 5-year follow up, 31/91 (34%) of the hysteropexy group met treatment failure criteria. All seven women who pursued reoperation reported bothersome prolapse symptoms; six were anatomic failures. Most seeking reoperation were early treatment failures; six (86%) by the 12-month visit and all by the 18-month visit. Compared to those electing expectant management, those pursuing reoperation had more apical prolapse, POP-Q point C median (IQR) -5.5 (-6.0, -4.0) cm versus +1.0 (-1.0, 3.0) cm respectively. Hysterectomy was performed in 6/7 reoperations (three vaginal, three endoscopic), with apical suspension in 5/6 hysterectomies. One participant with posterior compartment prolapse underwent transvaginal enterocele plication, uterosacral ligament suspension with posterior colpoperineorrhaphy. At a mean surgical follow-up of 34.3 (15.8) months, all women remained without anatomic or symptomatic failure. CONCLUSIONS: When recurrent prolapse after mesh hysteropexy occurred, most women did not choose reoperation. Those who pursued surgery experienced more significant apical prolapse and were universally symptomatic. CLINICAL TRIAL IDENTIFICATION NUMBER: NCT01802281.
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Prolapso de Órgão Pélvico , Prolapso Uterino , Feminino , Humanos , Procedimentos Cirúrgicos em Ginecologia , Prolapso de Órgão Pélvico/cirurgia , Recidiva , Reoperação , Retratamento , Telas Cirúrgicas/efeitos adversos , Resultado do Tratamento , Prolapso Uterino/cirurgiaRESUMO
Postpartum urinary retention (PUR) is a common and potentially morbid condition if not recognised and managed promptly. We surveyed obstetrics and gynaecology (OBGYN) residents to determine residents' knowledge of the management of PUR. A total of 168 OBGYN residents in ACGME accredited programmes in the United States completed the survey. A percentage of 30.3 reported having a PUR prevention protocol at their institution, 43.3% reported not having a protocol and 26.7% did not know whether a protocol existed. About 89.3% of participants reported having previously taken care of a patient with PUR and 17.1% reported prior formal teaching on the management of PUR. Those who reported having a protocol were more likely to report feeling comfortable managing PUR. Overall, knowledge was low for management of PUR. Given the potential morbidity associated with inadequate management of PUR, formal education and standardisation through national guidelines may help improve care of patients with PUR.Impact statementWhat is already known on this subject? PUR is a common condition and if left untreated may lead to long-term impacts on patients' health. Early recognition of the condition and appropriate management can prevent these complications. Protocols have been shown to improve patient outcomes. Thus, it has been postulated that the implementation of protocols could improve recognition of the condition.What do the results of this study add? No previous studies have looked at the impact of PUR management protocols on physicians in training. Because physicians in training are often the first-in-line to manage patients at academic institutions, we sought to determine the proportion of obstetrics and gynaecology residents in the United States who report having a PUR management protocol at their institution and how this impacts their reported comfort at caring for patients with PUR, knowledge on PUR risk factors and recognition of scenarios concerning for PUR. While awareness of a PUR protocol did not lead to increased knowledge of risk factors or increased recognition of scenarios concerning for PUR, it did increase resident comfort with managing PUR patients. We also found that overall PUR knowledge was low.What are the implications of these findings for clinical practice and/or further research? Based on our findings, OBGYN residents would benefit from having protocols at their institutions since it increased their comfort at managing patients with PUR. Further, formal education on PUR is likely needed to improve knowledge of risk factors and recognition of scenarios concerning for PUR.
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Competência Clínica/estatística & dados numéricos , Internato e Residência/estatística & dados numéricos , Obstetrícia/educação , Transtornos Puerperais , Retenção Urinária , Adulto , Gerenciamento Clínico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Gravidez , Inquéritos e Questionários , Estados UnidosAssuntos
Cistos/diagnóstico , Cistos Ovarianos/diagnóstico , Prolapso de Órgão Pélvico , Doenças Peritoneais/diagnóstico , Dor nas Costas , Anticoncepcionais Orais Combinados/uso terapêutico , Cistos/tratamento farmacológico , Cistos/cirurgia , Drenagem , Feminino , Humanos , Pessoa de Meia-Idade , Cistos Ovarianos/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Doenças Peritoneais/cirurgia , Recidiva , Tomografia Computadorizada por Raios XAssuntos
Adenossarcoma/patologia , Neoplasias do Endométrio/patologia , Prolapso de Órgão Pélvico/diagnóstico , Inversão Uterina/diagnóstico por imagem , Neoplasias Uterinas/patologia , Adenossarcoma/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Feminino , Humanos , Leiomiossarcoma , Pessoa de Meia-Idade , Neoplasias Uterinas/diagnóstico por imagem , Prolapso UterinoRESUMO
IMPORTANCE: No-show appointments, or scheduled appointments that patients do not attend without giving notice of cancellation, are a prevalent problem in the outpatient setting. OBJECTIVE: The objective of this study was to compare the proportion of patients by decades of life who "no-show" to their urogynecology appointments. STUDY DESIGN: This retrospective cohort included women 20 years and older who did not show to their urogynecologic clinical encounters at an academic practice between January 1, 2022, and December 31, 2022. Demographics and visit history were recorded. The primary outcome was the proportion of patients by decade of age who were a "no-show" to their appointments. All decades were compared with women in their 70s, the decade with the most patients seen. Secondary outcomes included descriptive data of patients. Descriptive statistics and χ2 analyses were used. RESULTS: The cohort of 450 no-show encounters (composed of 391 patients), out of 6729 encounters, demonstrated an overall no-show rate of 6.7%. Baseline demographics of "no-show" patients were 67.3% White and 27.4% Black. The odds of women in their 20s-50s who no-show was 2-3 times higher than women in their 70s (P < 0.01). The highest no-show rates occurred in 20s (12.6%) and 40s (11.8%). Forty-six patients missed multiple appointments. The odds of a Black patient having multiple no-shows was 3.15 times higher than the odds of a White patient. CONCLUSIONS: No-show rates are low in this urogynecology practice. Younger women are more likely to no-show. This knowledge can facilitate potential double bookings necessary for urgent appointments and to maximize resource utilization.
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Instituições de Assistência Ambulatorial , Pacientes não Comparecentes , Humanos , Feminino , Estudos Retrospectivos , Pacientes Ambulatoriais , TempoRESUMO
IMPORTANCE: It is crucial to understand the racial and ethnic disparities that exist in nocturia prevalence to appropriately manage nocturia. OBJECTIVES: Nocturia is associated with increased body mass index (BMI) and is most prevalent in Black and Hispanic women, who also have the highest and second highest prevalence of obesity, respectively. We sought to better understand the association of nocturia with BMI category by race and ethnicity in U.S. women. STUDY DESIGN: This was a cross-sectional study using publicly available data from the National Health and Nutrition Examination Survey data from 2005 to 2018. We estimated the prevalence of moderate to severe nocturia (defined as 2 or more episodes of nighttime urination) by BMI category within each racial and ethnic (Black, White, Hispanic, and other) group of adult women. Logistic regression was performed to determine the odds ratio of nocturia by race. RESULTS: The odds of nocturia was 2.25 (2.04-2.49) for Black women, 1.27 (1.15-1.4) for Hispanic women and 0.96 (0.82-1.13) for other women compared to White women. After accounting for BMI, socioeconomic status and comorbidities, the adjusted odds ratio was 1.76 (1.42-2.16) for Black women, 1.1 (.0.88-1.38) for Hispanic women, and 0.81 (0.5-1.29) for other women compared to White women. CONCLUSIONS: Black women were nearly twice as likely to have nocturia than White women. The increased odds of nocturia, while not sustained for Hispanic women, persisted for Black women regardless of socioeconomic status, BMI, and comorbidities. Our study suggests that there are factors other than weight driving the prevalence of nocturia in Black women that require further investigation.
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There is an urgent need to diversify the physician workforce in obstetrics and gynecology to serve a diverse patient population and mitigate disparities in care. There is a paucity of data on how to improve recruitment of individuals from underrepresented minoritized groups to the field of obstetrics and gynecology. This article outlines important steps for sharing the department's commitment to diversity, equity, and inclusion; addresses ways to attract a diverse applicant pool; and reviews the importance of and need to perform a holistic review of applicants. This commentary also shares some approaches to support faculty and trainees that may lead to sustained increases in diversity. Using this framework, the authors successfully increased the diversity of their obstetrics and gynecology residency program.
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Ginecologia , Internato e Residência , Obstetrícia , Médicos , Feminino , Gravidez , Humanos , Ginecologia/educação , Obstetrícia/educaçãoRESUMO
Despite a worldwide increase in obesity, little is known about obesity in Africa and factors related to attempting weight loss (AWL) in high-risk populations. The aims of this study were to determine the prevalence of obesity among patients in a Togolese cardiology clinic and determine predictors of reporting AWL and physician advice for weight loss. We recruited French-speaking men and women, aged > or = 18 years from this academic cardiology clinic to complete a questionnaire and anthropometric measurements. Among 135 patients, 33% were overweight and 24% were obese. Among overweight and obese patients (n = 76), logistic regression was used to calculate odds ratios (OR) for predictors of AWL and physician advice. 53% reported AWL and 49% received physician advice. Obese participants were 11 times more likely than overweight participants to report AWL (OR = 11.14; P < .0001). AWL was more common in those reporting physician advice (OR = 7.58; P = .0001) and women (OR = 2.78; P = .04). Obesity and female sex were also associated with reporting physician advice to lose weight. Age and education were not associated with AWL or physician advice. Physician advice highly correlates with AWL; however only half of participants received it. Physicians should make efforts to incorporate weight loss advice in their routine care.
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Aconselhamento , Sobrepeso/fisiopatologia , Redução de Peso , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Togo , Adulto JovemRESUMO
OBJECTIVES: This study aimed to determine if the location of a repaired bladder injury (trigone vs dome) impacts the probability of an abnormal cystography result in obstetric/gynecologic surgical patients undergoing repair of an unanticipated cystotomy. METHODS: We conducted a retrospective review of adult obstetric and gynecologic surgical patients who underwent cystographic evaluation of bladder integrity after repair of iatrogenic cystotomy at a single institution between January 2006 and July 2018. We excluded patients who had undergone repair of genitourinary fistula or urethral diverticulum. Patients were dichotomized into 2 groups based on the location of the repaired bladder injury: trigone versus dome. Fisher exact and Student t tests were used to determine the proportion of abnormal cystogram results and factors associated with an abnormal cystography result. RESULTS: Two hundred ten cases met the inclusion criteria: 176 in the dome group and 34 in the trigone group. When comparing the dome and trigone groups, respectively, mean age (45.2 ± 12.5 vs 48.4 ± 11.2 years) and cystotomy size (3.2 ± 3.2 vs 2.2 ± 2.4 cm) were comparable. Duration of postoperative bladder catheterization was longer in the trigone group (13.7 vs 12.1 days, P = 0.03). Despite the additional bladder drainage, there were more abnormal cystogram results in the trigone group versus the dome (8.8% vs 1.1%; odds ratio, 8.4). CONCLUSIONS: A repaired cystotomy at the trigone is associated with increased odds of an abnormal cystography result. An abnormal cystography result after repair at the bladder dome is rare.
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Cistografia , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/lesões , Adulto , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Bexiga Urinária/cirurgiaRESUMO
OBJECTIVE: To compare prolapse recurrence after total vaginal hysterectomy with uterosacral ligament suspension to recurrence after supracervical hysterectomy with mesh sacrocervicopexy for the primary management of uterovaginal prolapse. METHODS: We conducted a retrospective cohort study of women undergoing uterovaginal prolapse repair at an academic center from 2009 to 2019. Women who underwent vaginal hysterectomy with uterosacral ligament suspension or laparoscopic supracervical hysterectomy with mesh sacrocervicopexy were included. The primary outcome was composite prolapse recurrence (prolapse beyond the hymen or retreatment with pessary or surgery). Secondary outcomes included mesh complications, time to recurrence, and overall reoperation for either prolapse recurrence or mesh complication. We used propensity scoring with a 2:1 ratio of sacrocervicopexy to uterosacral suspension. RESULTS: The cohort consisted of 654 patients, of whom 228 (34.9%) underwent uterosacral suspension and 426 (65.1%) underwent sacrocervicopexy. The median follow-up was longer for the sacrocervicopexy group (230 vs 126 days, P<.001) and less than 1 year for both groups. The uterosacral group had a greater proportion of composite prolapse recurrence (14.9% [34/228] vs 8.7% [37/426], P=.02) and retreatment for recurrent prolapse (7.5% [17/228] vs 2.8% [12/426], P=.02). The uterosacral group demonstrated a shorter time to prolapse recurrence on multivariable Cox regression (hazard ratio 3.14, 95% CI 1.90-5.16). There were 14 (3.3%) mesh complications in the sacrocervicopexy group. Overall reoperation was similar between groups (4.8% [11/228] vs 3.8% [16/426], P=.51). CONCLUSION: Total vaginal hysterectomy with uterosacral ligament suspension was associated with higher rate of, and shorter time-to-prolapse recurrence compared with supracervical hysterectomy with mesh sacrocervicopexy.
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Prolapso Uterino/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Histerectomia Vaginal , Ligamentos/cirurgia , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Telas Cirúrgicas , Resultado do TratamentoRESUMO
BACKGROUND: Hypovolemic hyponatremia has not been widely reported in the obstetric literature. Anecdotally, we noticed severe hyponatremia in several of our patients who presented as home birth transfers, leading to a review of home birth cases and hyponatremia. Given the morbidity associated with hyponatremia, it is important to be aware of its potential occurrence. CASE: We present the cases of two patients transferred to our hospital with hyponatremia after prolonged labor. These women presented with altered mental status, somnolence, and decreased urine output. Both were admitted to the intensive care unit but made a full recovery. CONCLUSION: Hyponatremia is a serious potential complication of prolonged labor. We propose mechanisms for this condition and recommendations for surveillance and prevention.
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Parto Domiciliar , Hiponatremia/diagnóstico , Complicações do Trabalho de Parto/diagnóstico , Transferência de Pacientes , Assistência Perinatal , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Hiponatremia/terapia , Complicações do Trabalho de Parto/terapia , GravidezAssuntos
Prolapso de Órgão Pélvico , Saúde da Mulher , Humanos , Feminino , Prolapso de Órgão Pélvico/epidemiologia , Prolapso de Órgão Pélvico/etnologia , Pessoa de Meia-Idade , Incidência , Estados Unidos/epidemiologia , Etnicidade/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , AdultoRESUMO
Current assays of CD8+ T-lymphocyte function measure cytokine production rather than the ability of these lymphocytes to suppress viral replication. Here we show that CD8+ T-cell clones recognizing the same epitope vary enormously in the ability to suppress simian immunodeficiency virus SIVmac239 replication in an in vitro suppression assay. However, all Nef(165-173)IW9- and Vif(66-73)HW8-specific clones from elite controllers effectively suppressed SIV replication. Interestingly, in vitro suppression efficacy was not always associated with the ability to produce gamma interferon, tumor necrosis factor alpha, or interleukin-2.
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Linfócitos T CD8-Positivos/imunologia , Citocinas/biossíntese , Vírus da Imunodeficiência Símia/imunologia , Replicação Viral/imunologia , Animais , Macaca mulatta , Vírus da Imunodeficiência Símia/fisiologia , Carga Viral , Replicação Viral/fisiologiaRESUMO
"Elite controllers" are individuals that durably control human immunodeficiency virus or simian immunodeficiency virus replication without therapeutic intervention. The study of these rare individuals may facilitate the definition of a successful immune response to immunodeficiency viruses. Here we describe six Indian-origin rhesus macaques that have controlled replication of the pathogenic virus SIVmac239 for 1 to 5 years. To determine which lymphocyte populations were responsible for this control, we transiently depleted the animals' CD8+ cells in vivo. This treatment resulted in 100- to 10,000-fold increases in viremia. When the CD8+ cells returned, control was reestablished and the levels of small subsets of previously subdominant CD8+ T cells expanded up to 2,500-fold above pre-depletion levels. This wave of CD8+ T cells was accompanied by robust Gag-specific CD4 responses. In contrast, CD8+ NK cell frequencies changed no more than threefold. Together, our data suggest that CD8+ T cells targeting a small number of epitopes, along with broad CD4+ T-cell responses, can successfully control the replication of the AIDS virus. It is likely that subdominant CD8+ T-cell populations play a key role in maintaining this control.
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Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Vírus da Imunodeficiência Símia/fisiologia , Replicação Viral , Animais , Sequência de Bases , Linfócitos T CD4-Positivos/imunologia , Células Cultivadas , Técnicas de Cocultura , Epitopos de Linfócito T/imunologia , Produtos do Gene gag/imunologia , Variação Genética/genética , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Macaca mulattaRESUMO
CD8(+) T lymphocytes appear to play a role in controlling human immunodeficiency virus (HIV) replication, yet routine immunological assays do not measure the antiviral efficacy of these cells. Furthermore, it has been suggested that CD8+ T cells that recognize epitopes derived from proteins expressed early in the viral replication cycle can be highly efficient. We used a functional in vitro assay to assess the abilities of different epitope-specific CD8+ T-cell lines to control simian immunodeficiency virus (SIV) replication. We compared the antiviral efficacies of 26 epitope-specific CD8+ T-cell lines directed against seven SIV epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01 or Mamu-A*02. Suppression of SIV replication varied depending on the epitope specificities of the CD8+ T cells and was unrelated to whether the targeted epitope was derived from an early or late viral protein. Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T-cell lines were consistently superior at suppressing viral replication compared to the other five SIV-specific CD8+ T-cell lines. We also investigated the impact of viral escape on antiviral efficacy by determining if Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T-cell lines could suppress the replication of an escaped virus. Viral escape abrogated the abilities of Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T cells to control viral replication. However, gamma interferon (IFN-gamma) enzyme-linked immunospot and IFN-gamma/tumor necrosis factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant. Understanding antiviral efficacy and epitope variability, therefore, will be important in selecting candidate epitopes for an HIV vaccine.
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Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Vírus da Imunodeficiência Símia/imunologia , Linfócitos T/imunologia , Animais , Linhagem Celular , Células Cultivadas , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Produtos do Gene gag/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Macaca mulatta , Mutação Puntual , RNA Viral/sangue , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/fisiologia , Linfócitos T/química , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Carga Viral , Replicação Viral/genética , Replicação Viral/imunologiaRESUMO
The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4(+) memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.
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Produtos do Gene env/administração & dosagem , Imunidade Celular , Vacinas contra a SAIDS/farmacologia , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Anticorpos Antivirais/biossíntese , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Produtos do Gene env/imunologia , Imunização , Macaca mulatta , Vacinas contra a SAIDS/administração & dosagem , Carga Viral , Replicação ViralRESUMO
In the acute stage of infection following sexual transmission of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), virus-specific CD8+ T-lymphocyte responses partially control but do not eradicate infection from the lymphatic tissues (LTs) or prevent the particularly massive depletion of CD4+ T lymphocytes in gut-associated lymphatic tissue (GALT). We explored hypothetical explanations for this failure to clear infection and prevent CD4+ T-lymphocyte loss in the SIV/rhesus macaque model of intravaginal transmission. We examined the relationship between the timing and magnitude of the CD8+ T-lymphocyte response to immunodominant SIV epitopes and viral replication, and we show first that the failure to contain infection is not because the female reproductive tract is a poor inductive site. We documented robust responses in cervicovaginal tissues and uterus, but only several days after the peak of virus production. Second, while we also documented a modest response in the draining genital and peripheral lymph nodes, the response at these sites also lagged behind peak virus production in these LT compartments. Third, we found that the response in GALT was surprisingly low or undetectable, possibly contributing to the severe and sustained depletion of CD4+ T lymphocytes in the GALT. Thus, the virus-specific CD8+ T-lymphocyte response is "too late and too little" to clear infection and prevent CD4+ T-lymphocyte loss. However, the robust response in female reproductive tissues may be an encouraging sign that vaccines that rapidly induce high-frequency CD8+ T-lymphocyte responses might be able to prevent acquisition of HIV-1 infection by the most common route of transmission.
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Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T , Epitopos Imunodominantes , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vagina/virologia , Animais , Feminino , Interferon gama/biossíntese , Intestinos/imunologia , Tecido Linfoide/imunologia , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Replicação ViralRESUMO
Epitope-specific CD8+ T lymphocytes may play an important role in controlling human immunodeficiency virus (HIV)/simian immunodeficiency virus replication. Unfortunately, standard cellular assays do not measure the antiviral efficacy (the ability to suppress virus replication) of CD8+ T lymphocytes. Certain epitope-specific CD8+ T lymphocytes may be better than others at suppressing viral replication. We compared the antiviral efficacy of two immunodominant CD8+ T lymphocyte responses--Tat(28-35)SL8 and Gag(181-189)CM9--by using a functional in vitro assay. Viral suppression by Tat-specific CD8+ T lymphocytes was consistently greater than that of Gag-specific CD8+ T lymphocytes. Such differences in antigen-specific CD8+-T-lymphocyte efficacy may be important for selecting CD8+ T lymphocyte epitopes for inclusion in future HIV vaccines.
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Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Vírus da Imunodeficiência Símia/imunologia , Replicação Viral/imunologia , Animais , Epitopos de Linfócito T/química , Produtos do Gene gag/imunologia , Produtos do Gene tat/imunologia , Macaca mulatta , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/fisiologia , Replicação Viral/fisiologiaRESUMO
MHC class I-restricted CD8+ T cells play an important role in controlling HIV and SIV replication. In SIV-infected Indian rhesus macaques (Macaca mulatta), comprehensive CD8+ T cell epitope identification has only been undertaken for two alleles, Mamu-A*01 and Mamu-B*17. As a result, these two molecules account for virtually all known MHC class I-restricted SIV-derived CD8+ T cell epitopes. SIV pathogenesis research and vaccine testing have intensified the demand for epitopes restricted by additional MHC class I alleles due to the shortage of Mamu-A*01+ animals. Mamu-A*02 is a high frequency allele present in over 20% of macaques. In this study, we characterized the peptide binding of Mamu-A*02 using a panel of single amino acid substitution analogues and a library of 497 unrelated peptides. Of 230 SIVmac239 peptides that fit the Mamu-A*02 peptide-binding motif, 75 peptides bound Mamu-A*02 with IC50 values of < or = 500 nM. We assessed the antigenicity of these 75 peptides using an IFN-gamma ELISPOT assay with freshly isolated PBMC from eight Mamu-A*02+ SIV-infected macaques and identified 17 new epitopes for Mamu-A*02. The synthesis of five Mamu-A*02 tetramers demonstrated the discrepancy between tetramer binding and IFN-gamma secretion by SIV-specific CD8+ T cells during chronic SIV infection. Bulk sequencing determined that 2 of the 17 epitopes accumulated amino acid replacements in SIV-infected macaques by the chronic phase of infection, suggestive of CD8+ T cell escape in vivo. This work enhances the use of the SIV-infected macaque model for HIV and increases our understanding of the breadth of CD8+ T cell responses in SIV infection.