RESUMEN
Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average annual incidence was 0·13/million (95% confidence interval 0·10-0·16) of which 50·0% were male. Where reported, 70·3% of injuries occurred in the home/garden (45/64). Overall, 40·3% (31/77) cases were in people who inject drugs (PWID), including a cluster of 22 cases during 2003-2004. Where known (n = 68), only 8·8% were age-appropriately immunized. The overall case-fatality rate was 11·0% (9/82). All tetanus-associated deaths occurred in adults aged >45 years, none of whom were fully immunized. Due to the success of the childhood immunization programme, tetanus remains a rare disease in England with the majority of cases occurring in older unimmunized or partially immunized adults. Minor injuries in the home/garden were the most commonly reported likely sources of infection, although cases in PWID increased during this period. It is essential that high routine vaccine coverage is maintained and that susceptible individuals, particularly older adults, are protected through vaccination and are offered timely post-exposure management following a tetanus-prone wound.
RESUMEN
Indigenously acquired hepatitis E infections have increased substantially in England and Wales since 2010. Epidemiological investigations were undertaken to determine risk factors for the acquisition of infection. A case-control study (25 cases, 75 controls) was used to test the hypothesis that hepatitis E infection was related to consumption of pork products. In a multivariable model, consumption of pork pie [odds ratio (OR) 6·33, 95% confidence interval (CI) 1·41-28·48, P = 0·009] and consumption of ham and sausages purchased from a major UK supermarket chain (OR 10·12, 95% CI 1·68-60·81, P = 0·023) were significantly associated with indigenous infection. The consumption of sausages and ham purchased from the supermarket was highly correlated; however. separate models showed that each variable was significantly associated with infection (OR 7·59, 95% CI 1·81-31·84, P = 0·004 and OR 10·98, 95% CI 1·84-65·35, P = 0·003, respectively). Although contamination of sausages with HEV has previously been shown this study also raises concerns about other processed pork products and whether current practice in preparing these products is sufficient to prevent transmission of HEV.
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Hepatitis E/epidemiología , Hepatitis E/transmisión , Productos de la Carne/virología , Adulto , Anciano , Animales , Estudios de Casos y Controles , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Porcinos , Gales/epidemiología , Adulto JovenRESUMEN
We describe here the United Kingdom (UK) response following the recent international recall of an organ preservation fluid owing to potential Bacillus cereus contamination. This fluid is used for the transport of solid organs and pancreatic islet cells for transplant. We detail the response mechanisms, including the initial risk stratification, investigatory approaches, isolate analysis and communications to professional bodies. This report further lays out the potential need for enhanced surveillance in UK transplant patients.
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Bacillus cereus , Contaminación de Medicamentos , Soluciones Preservantes de Órganos , Infecciones por Bacillaceae/epidemiología , Infecciones por Bacillaceae/microbiología , Bacillus cereus/aislamiento & purificación , Seguridad de Productos para el Consumidor , Electroforesis en Gel de Campo Pulsado , Humanos , Reino UnidoRESUMEN
Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom, from the Gulf region of the Middle East.
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Infecciones por Coronavirus/diagnóstico , Coronavirus/aislamiento & purificación , Transferencia de Pacientes , Síndrome Respiratorio Agudo Grave/etiología , Viaje , Animales , Coronavirus/clasificación , Coronavirus/patogenicidad , Infecciones por Coronavirus/microbiología , Infecciones por Coronavirus/virología , Notificación de Enfermedades , Reservorios de Enfermedades , Perfilación de la Expresión Génica , Humanos , Unidades de Cuidados Intensivos , Londres , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Insuficiencia Respiratoria/complicaciones , Insuficiencia Respiratoria/terapia , Arabia Saudita , Sensibilidad y Especificidad , Síndrome Respiratorio Agudo Grave/microbiología , Síndrome Respiratorio Agudo Grave/terapiaRESUMEN
On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.
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Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Coronavirus/aislamiento & purificación , Práctica de Salud Pública , Síndrome Respiratorio Agudo Grave/diagnóstico , Viaje , Adulto , Infecciones por Coronavirus/virología , Humanos , Londres , Masculino , Arabia Saudita , Síndrome Respiratorio Agudo Grave/virología , Reino UnidoAsunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales/inmunología , Humanos , Inmunidad Humoral , ReinfecciónRESUMEN
BACKGROUND: The largest outbreak of Ebola virus disease (EVD) is ongoing in West Africa. Air-travel data indicate that outside Africa, the UK is among the countries at greatest risk of importing a case of EVD. Hospitals in England were therefore instructed to prepare for the assessment and early management of suspected cases. However, the response of hospitals across England is undetermined. AIM: To evaluate the readiness of acute hospitals in England, and to describe the challenges experienced in preparing for suspected cases of EVD. METHODS: A cross-sectional study using semi-structured telephone interviews and online surveys of all acute National Health Service (NHS) hospital trusts in England (hospital trusts are the vehicle by which one or more NHS hospitals in a geographical area are managed). FINDINGS: In total, 112 hospital trusts completed the survey. All interviewed hospital trusts reported undertaking preparedness activities for suspected cases of EVD, and 97% reported that they were ready to assess suspected cases. Most hospital trusts had considered scenarios in accident & emergency (97%). However, fewer hospital trusts had considered specific obstetric (61%) and paediatric scenarios (79%), the provision of ventilatory and renal support (75%), or resuscitation in the event of cardiorespiratory arrest (56%). Thirty-four hospital trusts reported issues with timely access to category A couriers for sample transportation. Challenges included the choice, use and procurement of personal protective equipment (71%), national guidance interpretation (62%) and resource allocation/management support (38%). CONCLUSION: English hospital trusts have engaged well with EVD preparedness. Although subsequent national guidance has addressed some issues identified in this study, there remains further scope for improvement, particularly in a practical direction, for acute care services encountering suspected cases of EVD.
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Planificación en Desastres/organización & administración , Brotes de Enfermedades/prevención & control , Fiebre Hemorrágica Ebola/terapia , Administración Hospitalaria/métodos , Programas Nacionales de Salud/organización & administración , Estudios Transversales , Planificación en Desastres/métodos , Inglaterra/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/transmisión , Humanos , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
Peripheral B lymphocytes of five CLL patients were tested in a radioimmunoassay to determine the density of the C3b receptor (CR1) and the cells were assayed for their ability to mature into IgM secreting cells after in-vitro culture with a combination of Pokeweed Mitogen (PWM) and antibodies directed against CR1. Despite the presence of normal amounts of CR1 on the leukemic B cells, crosslinking of these receptors by anti-CR1 antibodies stimulated only a fraction of the leukemic cell population to differentiate into IgM secreting cells. These results add to the partial functional impairment of CLL-B cells.
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Anticuerpos/inmunología , Linfocitos B/inmunología , Leucemia Linfoide/patología , Activación de Linfocitos , Receptores de Complemento/inmunología , Linfocitos B/metabolismo , Linfocitos B/patología , Humanos , Inmunoglobulina M/metabolismo , Leucemia Linfoide/inmunología , Activación de Linfocitos/efectos de los fármacos , Mitógenos de Phytolacca americana/farmacología , Receptores de Complemento 3bRESUMEN
Following the report of the Centre for Evidence-based Purchasing, which suggested poor performance of Clostridium difficile testing kits, revised guidance was issued by the Department of Health (England) recommending a two-test algorithm. The aim of this study was to survey English National Health Service (NHS) diagnostic microbiology laboratories using an electronic questionnaire to investigate changes in laboratory procedures in response to the guidance and model the impact these changes had on national and locally reported data. It was found that 24% of laboratories had changed testing procedures and there was no evidence of an overall effect on the English mandatory surveillance data used for performance management. It was shown that there could be an impact on an individual NHS Trust's case numbers, and a simple model for Trusts to predict these changes in C. difficile laboratory diagnosis was developed. There was also evidence of the use of variable sample selection criteria, which could affect the positive and negative predictive values of local testing.
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Técnicas de Laboratorio Clínico/métodos , Clostridioides difficile/aislamiento & purificación , Enterocolitis Seudomembranosa/diagnóstico , Enterocolitis Seudomembranosa/epidemiología , Notificación Obligatoria , Inglaterra/epidemiología , Enterocolitis Seudomembranosa/microbiología , Humanos , Incidencia , Encuestas y CuestionariosRESUMEN
We have developed a new ELISA for detection of anti-schistosome antibodies using an extract from Schistosoma mansoni cercariae. We evaluated the new assay on serum samples sent to the Hospital for Tropical Diseases, Department of Clinical Parasitology, London, UK, by comparing it with our routinely used S. mansoni soluble egg antigen (SEA) assay. We also evaluated the new assay for cross-reactivity with a number of helminth and other infections. We demonstrate that the cercarial antigen assay is equivalent to the SEA assay for serodiagnosis of schistosomiasis in a non-endemic setting. The cercarial antigen preparation is more easily produced than SEA, and for this reason this assay may be preferred for routine clinical use and may be amenable to scaling up. Further assessment is needed before it can be recommended for use in an endemic area, as chronic disease and co-infection with other helminths are likely to be under-represented in our sample set.
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Antígenos Helmínticos , Ensayo de Inmunoadsorción Enzimática/métodos , Schistosoma mansoni/inmunología , Esquistosomiasis/diagnóstico , Animales , Antígenos Helmínticos/inmunología , Humanos , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis/inmunología , Sensibilidad y EspecificidadAsunto(s)
Linfocitos B/inmunología , Genes MHC Clase II/efectos de los fármacos , Antígenos de Histocompatibilidad/biosíntesis , Interleucina-4/farmacología , Cloruro de Mercurio/farmacología , Animales , Anticuerpos Monoclonales/farmacología , Linfocitos B/efectos de los fármacos , Células Cultivadas , Femenino , Interleucina-4/inmunología , Interleucina-4/fisiología , Ganglios Linfáticos/inmunología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Especificidad de la EspecieAsunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/biosíntesis , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/efectos de los fármacos , Fosfomicina/farmacología , Infecciones Urinarias/microbiología , beta-Lactamasas/biosíntesis , Enterobacteriaceae/enzimología , Enterobacteriaceae/aislamiento & purificación , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Human B cell subpopulations can be distinguished by the expression of B cell-associated antigens. mAb directed against these structures allow the isolation and subsequent functional analysis of such subsets. Blood B cells from healthy individuals were separated on basis of the expression of the antigens recognized by the mAb HB4 and FMC7. The B cells present in the thus obtained populations were analyzed for their ability to secrete IgM and IgG after stimulation in vitro with polyclonal B cell activators (PWM, Staphylococcus aureus Cowan I), antigens (tetanus toxoid, type 4 pneumococcal polysaccharides), and soluble B cell differentiation factors. The results suggest that B cells capable of Ig and anti-tetanus toxoid or anti-type 4 pneumococcal polysaccharide antibody production after in vitro culture are localized in a relative small B cell subpopulation carrying the FMC7 determinant but lacking HB4. This holds true for both the IgM- and IgG-secreting B cells. These data further suggest that the majority of B cells found in the blood and which can be characterized as being surface IgM+/IgD+ HB4+ are immature cells unable to respond to differentiation-inducing signals.
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Anticuerpos Monoclonales , Antígenos de Diferenciación de Linfocitos B/análisis , Linfocitos B/clasificación , Adulto , Anticuerpos Monoclonales/fisiología , Reacciones Antígeno-Anticuerpo , Linfocitos B/inmunología , Separación Celular , Citotoxicidad Inmunológica , Humanos , Activación de Linfocitos , Polisacáridos Bacterianos/inmunología , Polisacáridos Bacterianos/farmacología , Toxoide Tetánico/inmunología , Toxoide Tetánico/farmacologíaRESUMEN
In this study the idiotype-positive B cells of one patient with smouldering multiple myeloma (IgG kappa) and of one patient with multiple myeloma (IgG lambda) were analysed phenotypically and functionally. As regards the expression of B cell-associated differentiation antigens and size distribution, the idiotype-positive B cells resembled normal IgG-bearing blood B cells. In functional studies the lymphocytes were cultured in vitro with Staphylococcus aureus, pokeweed mitogen, T-cell factors, or combinations of these. After culture, proliferation and differentiation of the idiotype-positive B cells were measured by autoradiography, an idiotype-specific ELISA, and a spot ELISA. The results show that idiotype-positive B cells of both patients are able to proliferate after stimulation in vitro. In contrast to their normal counterparts, however, almost no increase in the amount of secreted idiotype IgG could be induced. This suggests that the idiotype-positive blood B cells have lost some of their ability to respond to exogenous stimuli.
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Linfocitos B/clasificación , Idiotipos de Inmunoglobulinas , Mieloma Múltiple/sangre , Antígenos de Diferenciación de Linfocitos B/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Linfocitos B/inmunología , Linfocitos B/metabolismo , Antígenos CD2 , Complejo CD3 , Citoplasma/análisis , Antígenos HLA-DR/análisis , Humanos , Inmunoglobulina G/biosíntesis , Idiotipos de Inmunoglobulinas/análisis , Activación de Linfocitos , Mieloma Múltiple/inmunología , Fenotipo , Receptores de Antígenos de Linfocitos T/análisis , Receptores Inmunológicos/análisisRESUMEN
The monoclonal B cells present in the blood of three patients with Waldenstrøm's macroglobulinaemia were analysed according to phenotype and function. As a marker for the monoclonal nature of the detected immunoglobulin (Ig) molecules, the kappa/lambda-ratio (two patients) or the presence of idiotypic (Id) determinants (one patient) were used. With double immunofluorescence it was shown that the neoplastic blood B cells were heterogeneous in respect to maturation stage. In addition to B cells carrying membrane bound IgM and IgD (mIgM+/IgD+), both mIgM+/IgD- and cytoplasmic IgM+ blastoid cells could be detected in the blood of the patients. This heterogeneity was also reflected in the responses of the monoclonal B cells upon stimulation with mitogens and T cell factors. B blastoid cells and IgM secretion could be induced after in vitro culture in the presence of Staphylococcus aureus, Pokeweed mitogen or a combination of both mitogens. It was shown that also T cell factors were effective in inducing monoclonal B cell differentiation.
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Linfocitos B/inmunología , Inmunoglobulina M/análisis , Activación de Linfocitos , Células Plasmáticas/inmunología , Macroglobulinemia de Waldenström/inmunología , Células Cultivadas , Células Clonales , Humanos , Interleucina-2/inmunología , Fenotipo , Mitógenos de Phytolacca americana/farmacología , Staphylococcus aureus/inmunologíaRESUMEN
Borderline leprosy patients often undergo acute changes in immune reactivity that manifest as reversal reaction (RR) in the course of the disease. RR is associated with an exacerbated local delayed-type cellular immune response to Mycobacterium leprae and is responsible for severe tissue damage. We investigated whether RR episodes are associated with a change in T cell subsets in the lesional skin with regard to their cytokine secretion profiles. M. leprae-responsive T cell lines and thereafter T cell clones (TCC) were generated from the lesional skin of seven untreated borderline leprosy patients (with or without RR) and again from three of these patients experiencing RR during treatment. The phenotypes of the M. leprae-responsive TCC were either CD4+, CD8+, CD4-/CD8+/TCR gammadelta+, or CD4-/CD8-/TCR gammadelta+, although most of them were CD4+. Regardless of the clinical status of the untreated patients, a major subset of the M. leprae-responsive TCC was type 0-like and produced both IFN-gamma and IL-4. Interestingly, in all three patients who experienced a (re)occurrence of RR during treatment after the first analysis, a clear shift to polarized IFN-gamma production by the M. leprae-responsive TCC (type 1-like) was observed. This shift in T cell subsets was also reflected in the observed decrease in serum IgG and IgM levels of the same patients during RR. These finding indicate that CD4+ M. leprae-responsive T cells with a polarized type 1-like phenotype might be responsible for the immune-mediated tissue damage occurring during RR.
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Citotoxicidad Inmunológica , Lepra Dimorfa/inmunología , Mycobacterium leprae/inmunología , Subgrupos de Linfocitos T/inmunología , Citocinas/biosíntesis , Citocinas/inmunología , Humanos , Inmunofenotipificación , Lepra Dimorfa/patología , Piel/inmunología , Piel/patologíaRESUMEN
CD134 (OX40), a member of the tumour necrosis factor receptor family, is expressed on activated T cells and mediates T and B cell costimulation. Its expression is increased after exposure to the thiol-binding compound HgCl2 in BN rats, but not in Lewis rats, in association with induction of a T cell-dependent systemic autoimmune syndrome only in BN rats. Intracellular thiols are involved in regulation of activation and death in T lymphocytes. Therefore, we examined intracellular thiol levels in CD134-defined T cell subsets from BN and Lewis rats. Levels of total thiols and glutathione (GSH) were significantly higher in CD134+CD4+ cells than in CD134+CD4+ cells in both strains. In Lewis rats, total thiol levels in CD4+CD134+ cells, but not in CD4+CD134+ cells, were higher than in BN rats. In contrast, BN rats showed higher GSH levels in CD4+CD134+ cells, but not in CD4+CD134+ cells. In vitro exposure to HgCl2 decreased intracellular thiol levels, predominantly in CD4+CD134+ cells. Furthermore, HgCl2-induced enrichment of CD134+ viable cells was inversely correlated to HgCl2-induced cell death. Strain-dependent differences in thiol levels in CD134-defined subsets of CD4+ lymphocytes and subset-specific modification of thiol levels may contribute to differential lymphocyte activation by oxidizing chemicals.
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Glutatión/metabolismo , Cloruro de Mercurio/farmacología , Receptores del Factor de Necrosis Tumoral , Compuestos de Sulfhidrilo/metabolismo , Subgrupos de Linfocitos T/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/biosíntesis , Animales , Antígenos CD4/biosíntesis , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Citometría de Flujo , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Receptores OX40 , Especificidad de la Especie , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/metabolismo , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunologíaRESUMEN
Susceptibility to induction of both T helper 1- (Th1) and Th2-mediated autoimmunity is multifactorial and involves genetic linkage to the major histocompatibility complex (MHC) class II haplotype. Brown Norway (BN) rats exposed to mercuric chloride develop a Th2-dependent systemic autoimmunity, whereas Lewis rats, which are highly susceptible to Th1-mediated autoimmunity, develop immune suppression after mercuric chloride exposure. Exposure to mercuric chloride is known to enhance B-lymphocyte expression of the MHC class II molecule RT1.B, predominantly in BN rats. We demonstrate that, in contrast, expression of RT1.D was unmodified on these B cells, whereas both RT1.B and RT1.D were up-regulated on epithelial cells. Regulation of B-cell MHC class II isotype expression was further studied in vitro, using BN rat lymph node (LN) cells. Interleukin-4 (IL-4) strongly enhanced B-cell expression of RT1.B (2.8-fold), whereas RT1.D expression was only slightly, although significantly, modified (1.2-fold). B cells from Lewis rats showed a similar IL-4-induced enhancement of RT1.B expression (2.5-fold), whereas, in contrast, RT1.D expression was unmodified. Exposure of LN cells from BN rats to interferon-gamma induced a moderate increase of B-cell MHC class II expression, predominantly of RT1.B. Strong and rapid enhancement of B-cell RT1.D expression was observed after stimulation by phorbol 12-myristate 13-acetate and ionomycin. Rat IL-13 did not modify B-cell MHC class II expression; however, it induced typical morphological changes in peritoneal macrophages. These experiments demonstrate isotype-specific and strain-dependent regulation of MHC class II expression on rat B lymphocytes, which may be of pathophysiological relevance for the strain-dependent susceptibility for Th1- or Th2-mediated autoimmunity.
Asunto(s)
Linfocitos B/inmunología , Citocinas/inmunología , Antígenos de Histocompatibilidad/metabolismo , Animales , Técnicas de Cultivo de Célula , Regulación de la Expresión Génica/inmunología , Técnicas para Inmunoenzimas , Interferón gamma/inmunología , Interleucina-13/inmunología , Interleucina-4/inmunología , Ionomicina/inmunología , Cloruro de Mercurio/inmunología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas Lew , Proteínas Recombinantes/inmunología , Acetato de Tetradecanoilforbol/inmunologíaRESUMEN
In an earlier study, we generated a large number of Mycobacterium leprae-responsive and M. leprae-nonresponsive T cell clones (TCC) from the lesional skin of immunologic unstable borderline leprosy patients. In that study, we divided TCC into type 1- and type 2-like on the basis of their IFN-gamma and IL-4 expression. To explore whether other cytokines are coproduced along with IFN-gamma and IL-4, we investigated the secretion of a panel of other cytokines (TNF-alpha, IL-5, IL-6, IL-10, and IL-13) by a large number of these TCC. Upon analysis of 139 M. leprae-responsive TCC, we observed a positive correlation in the coproduction of IFN-gamma/TNF-alpha (r = 0.81), and in that of IL-4/IL-5 (r = 0.83), IL-4/IL-13 (r = 0.80), and IL-5/IL-13 (r = 0.82). Polarized type 1-like TCC produced dominantly IFN-gamma/TNF-alpha, and polarized type 2-like TCC predominantly IL-4/IL-5/IL-13. Most type 0-like TCC produced both sets of cytokines. In contrast, type 1- and type 2-like subsets of M. leprae-nonresponsive TCC (n = 58) did not show the same coexpression of these cytokines. Furthermore, when the differential expression of a broad panel of cytokines by individual M. leprae-responsive TCC is considered, it appeared that additional phenotypes could be recognized. These results suggested that distinct isotypes of type 1- and type 2-like T cells, based on the secretion of a panel of cytokines, may reflect M. leprae-specific characteristics.