CMV exposure drives long-term CD57+ CD4 memory T-cell inflation following allogeneic stem cell transplant.

Donor and recipient cytomegalovirus (CMV) serostatus correlate with transplant-related mortality that is associated with reduced survival following allogeneic stem cell transplant (SCT). Prior epidemiologic studies have suggested that CMV seronegative recipients (R-) receiving a CMV-seropositive graft (D+) experience inferior outcomes compared with other serostatus combinations, an observation that appears independent of viral reactivation. We therefore investigated the hypothesis that prior donor CMV exposure irreversibly modifies immunologic function after SCT. We identified a CD4+/CD57+/CD27- T-cell subset that was differentially expressed between D+ and D- transplants and validated results with 120 patient samples. This T-cell subset represents an average of 2.9% (D-/R-), 18% (D-/R+), 12% (D+/R-), and 19.6% (D+/R+) (P < .0001) of the total CD4+ T-cell compartment and stably persists for at least several years post-SCT. Even in the absence of CMV reactivation post-SCT, D+/R- transplants displayed a significant enrichment of these cells compared with D-/R- transplants (P = .0078). These are effector memory cells (CCR7-/CD45RA+/-) that express T-bet, Eomesodermin, granzyme B, secrete Th1 cytokines, and are enriched in CMV-specific T cells. These cells are associated with decreased T-cell receptor diversity (P < .0001) and reduced proportions of major histocompatibility class (MHC) II expressing classical monocytes (P < .0001), myeloid (P = .024), and plasmacytoid dendritic cells (P = .0014). These data describe a highly expanded CD4+ T-cell population and putative mechanisms by which prior donor or recipient CMV exposure may create a lasting immunologic imprint following SCT, providing a rationale for using D- grafts for R- transplant recipients.

Favorable prognostic impact of Natural Killer cells and T cells in high-grade serous ovarian carcinoma.

Introduction: The aim of the present study was to investigate the prognostic impact of intratumoral cytotoxic T cells, Natural Killer (NK) cells, neutrophils and PD-L1 expression in patients with epithelial ovarian cancer.Methods: All patients diagnosed with high-grade serous carcinoma (HGSC) in Denmark in 2005 were included in the study. Immunohistochemical staining for PD-L1, CD8, CD66b and CD57 was performed on tumor tissue from 283 patients. Cell densities were analyzed using a digital image analysis method. The primary endpoint was overall survival (OS).Results: The median OS for HGSC patients was 30 months. It was 45 months in patients with high level of CD57+ NK cells (≥10 cells/mm2) compared with 29 month in patients with low level (<10 cells/mm2) (p = .0310). The median OS was 37 and 25 months in patients with high vs. low level of CD8+ T cells (cutoff 80 cells/mm2) (p = .0008). In multivariate analysis, high numbers of CD57+ NK cells and CD8+ T cells remained independent markers of favorable OS, adjusted hazard ratio (HR) 0.67; p = .041, and HR 0.72; p = .020, respectively. PD-L1 expression was associated with improved OS (37 months vs. 22 months, p = .0006), but was only borderline significant in the multivariate analysis (HR 0.77, p = .061). CD66b + neutrophils had no association with OS.Conclusions: In patients with HGSC tumor-infiltrating CD57+ NK cells and CD8+ T cells had favorable prognostic impact, while PD-L1 expression had borderline favorable prognostic significance. CD66b + neutrophils had no prognostic association. These findings may influence future immunotherapy development.

Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers.

Cytolytic CD4+ T cells play a prominent role in chronic viral infection. CD4+ CTLs clones specific for HIV-1 Nef and Gag are capable of killing HIV-1 infected CD4+ T cells and macrophages. Additionally, HIV-specific cytolytic CD4+ T cell responses in acute HIV infection are predictive of disease progression. CD57 expression on CD4s identifies cytolytic cells. These cells were dramatically increased in chronic HIV infection. CD57 expression correlated with cytolytic granules, granzyme B and perforin expression. They express lower CCR5 compared to CD57- cells, have less HIV total DNA, and were a minor component of the HIV reservoir. A small percentage of CD57+ CD4+ CTLs from EC were HIV-specific, could upregulate IFNγ with Gag peptide stimulation, express cytolytic granule markers and maintain TbethighEomes+ transcription factor phenotype. This was not observed in viraemic controllers. The maintenance of HIV-specific CD4 cytolytic function in Elite controllers together with CD8 CTLs may be important for the control of HIV viraemia and of potential relevance to cure strategies.

[The histopathology and immunohistochemistry of granular cell tumour. A study of 12 cases with a brief historical note]. / Análisis histopatológico e inmunohistoquímico del tumor de células granulares. Estudios de 12 casos con una breve nota histórica.

INTRODUCTION AND OBJECTIVE: Granular cell tumour (GCT) is a benign neoplasm of neural/schwannian origin, usually presenting as a single asymptomatic lesion, mainly located in the dermis and subcutaneous tissue or submucosa, although multiple tumours may occur. Microscopically, GCTs are composed of large cells with abundant eosinophilic, granular cytoplasm arranged in sheets, nests, cords or trabeculae. Based on the cytological characteristics and the presence of necrosis, three types are recognized: benign, atypical and malignant. We aim to present the cytological and immunohistochemical characteristics of 12 granular cell tumours. MATERIALS AND METHODS: 12 cases of GCT were selected from the consultation files of one of the authors (COH) The paraffin embedded tissue was processed for immunostaining with S-100 protein, calretinin, CD68, α-inhibin, PGP9.5, CD57 (Leu7), CD63 (NKI / C3), Gap43 (growth-associated protein-43), SOX10, TFE-3 and Ki-67. RESULTS AND CONCLUSIONS: 6 male and 6 female patients, with an average age of 40, made up the study group. The most frequent location for the tumours was in the subcutaneous soft tissues of the arms. There were no malignant cases. All tumours were positive for S-100, CD57, SOX10, calretinin, CD68, PGP9.5, α-inhibin and TFE-3, with a low Ki-67 (1-5%). Additionally, we reported, for the first time, the positive immunoreaction to Gap43 (growth-associated protein-43) in GCT.

Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma.

The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index, apoptotic index, and microvessel density were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multivariate analyses (hazard ratio = 1.41, 95% confidence interval = 1.03-1.93, P = .031) and was significantly correlated with proliferation index, apoptotic index, and microvessel density (r = .47, P <. 001; r = -.31, P < .001; and r = .40, P < .001, respectively). In conclusion, CD57+ cells, CD68+ cells, and mast cells played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis.

Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts.

The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

Analysis of CD15, CD57 and HIF-1α in biopsies of patients with peri-implantitis.

Peri-implantitis is an infectious disease characterized by inflammation of the tissues surrounding the implant, bleeding on probing with or without suppuration, and bone loss. Peri-implant lesions contain a leukocyte infiltrate of plasma cells, lymphocytes, macrophages and neutrophils. A survey of the literature did not show any studies reporting an association between hypoxia and peri-implantitis. The aim of the present cross-sectional study was to evaluate histological changes and immunostaining for CD15, CD57 and HIF-1α in the peri-implant mucosa of patients with and without peri-implantitis. Mucosal biopsies were obtained from 18 patients with peri-implantitis and 10 control subjects without peri-implantitis at a private health care center between 2010 and 2012. The sections were fixed in 10% buffered formalin, processed and embedded in paraffin for histopathological and immunohistochemical study. Acanthosis, spongiosis and exocytosis were observed in both groups, with no significant difference between them. The peri-implantitis group showed increased immunostaining for CD15, a neutrophil marker, and HIF-1α, a tissue hypoxia marker, but no significant difference in immunostaining for CD57, a Natural Killer cell marker. The increase in neutrophil (CD15) and hypoxia (HIF-1α) markers in patients with peri-implantitis suggests an active participation of neutrophils and hypoxia in the pathogenesis of this disease. Since the present study was the first to evaluate the expression of CD15, CD57 and HIF-1α in peri-implant tissues, further studies should be performed to better understand the role of these molecules in peri-implantitis.

NK cells generate memory-type responses to human cytomegalovirus-infected fibroblasts.

Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C+ CD57+ NK cells in vivo and NKG2C+ NK cells proliferate when cultured with HCMV-infected cells. This raises the possibility of an NK-cell subset selectively responding against a specific pathogen and accruing memory. To test this possibility, we compared proliferation, natural cytotoxicity and interferon-γ (IFN-γ) production of NK cells from HCMV-seropositive and HCMV-seronegative individuals co-cultured with HCMV-infected or uninfected MRC-5 cells. There was no significant difference in proliferation of NK cells from HCMV-seropositive or seronegative individuals against uninfected MRC-5 cells, but significantly more NK cells from the HCMV-seropositive group proliferated in response to HCMV-infected MRC-5 cells. Natural cytotoxicity of NK cells against K562 cells increased following co-culture with HCMV-infected versus uninfected MRC-5 only for the HCMV-seropositive group. After co-culture with HCMV-infected MRC-5 cells, proliferating NK cells from HCMV-seropositive donors selectively produced IFN-γ when re-exposed to HCMV-infected MRC-5 cells. Both NKG2C+ and NKG2C- NK cells proliferated in co-culture with HCMV-infected MRC-5 cells, with the fraction of proliferating NKG2C+ NK cells directly correlating with the circulating NKG2C+ fraction. These data illustrate an at least partly NKG2C-independent human NK-cell memory-type response against HCMV.

Cytomegalovirus infection alters phenotypes of different γδ T-cell subsets in renal transplant recipients with long-term stable graft function.

Cytomegalovirus (CMV) infection alters the phenotypic profiles of T-cells and NK cells in healthy and immunocompromised individuals. Here, we examined the effects of CMV infection on the phenotype and functions of γδ T-cell subsets in renal transplant recipients (RTR) stable several years after transplantation (n = 80) and healthy controls (n = 72). Differentiation status, function, and expression of HLA-DR, CD57, and LIR-1 on Vδ2- and Vδ2+ γδ T-cells were examined in peripheral blood cells using flow cytometry. Percentages of Vδ2- γδ T-cells were higher in RTR who are CMV-seropositive and correlated with CMV antibody levels. Proportions of Vδ2- γδ T-cells expressing HLA-DR, CD57, or LIR-1 were increased in CMV-seropositive RTR and healthy controls compared to their seronegative counterparts. Additionally, Vδ2- γδ T-cells were skewed towards a terminally differentiated phenotype and most expressed CD8 in individuals who were CMV-seropositive. Increased expression of LIR-1 on terminally differentiated Vδ2- γδ T-cells was associated with CMV seropositivity in RTR and controls. The presence of CMV DNA in 15 RTR was associated with higher frequencies of LIR-1+ Vδ2+ γδ T-cells and increased percentages of terminally differentiated effector memory cells in both γδ T-cell subsets. Our study further characterises the effects of CMV and transplantation on γδ T-cell phenotypes.

American cutaneous leishmaniasis: In situ immune response of patients with recent and late lesions.

TNF-α, IFN-γ, IL-10, IL-17, CD68 and CD57 were evaluated in biopsies of patients with American cutaneous leishmaniasis living in Sorocaba, Brazil. The analyses were performed considering the time of lesions from 23 patients with recent lesions (Group I) and 19 patients with late lesions (Group II). All patients were infected with Leishmania (Viannia) braziliensis. Immunostaining cells for CD68, CD57, TNF- α, IFN-γ, IL-10 and IL-17 were performed by immunohistochemistry. Except for CD68 and IL-17, the distribution of in situ for CD57, IL-10, TNF-α and IFN-γ showed that patients with recent lesions expressed higher levels than those with late lesions. The comparison of cytokine expression/group showed that IL-10 was significantly higher than IL-17 and IFN-γ (similar data were shown in IL-17 compared with TNF-α), suggesting an immunological balance between inflammatory-anti-inflammatory agents. This balance was similar for two groups of patients. In conclusion, these data suggested that (i) patients from Group I had recent lesions (in the beginning of chronic phase) compared to those from Group II and (ii) the modulation of inflammatory response in patients with recent American cutaneous leishmaniasis was correlated with IL-10 expression in skin lesions preventing the development of mucosal forms. The parasite treatment also prevented the evolution of severe forms.

Analysis of CD57+ natural killer cells and CD8+ T lymphocytes in periapical granulomas and radicular cysts

Abstract: The aim of this study was to compare the number of CD57+ natural killer (NK) cells and CD8+ T lymphocytes between periapical granulomas (PGs) and radicular cysts (RCs). Twenty-fives cases of PGs and 25 of RCs were submitted to histological analysis and immunohistochemistry using anti-CD57 and anti-CD8 biomarkers. Positive cells were counted in 10 fields (400× magnification) and the median value was calculated for each case. Statistical tests were used to evaluate differences in the number of CD57+ NK cells and CD8+ T lymphocytes according to type of lesion, intensity of the infiltrate and thickness of the lining epithelium. The number of CD57+ NK cells and CD8+ T lymphocytes was higher in PGs than in RCs (p = 0.129 and p = 0.541, respectively). Comparison of the number of CD57+ NK cells in atrophic and hyperplastic epithelium revealed a larger number of cells in the atrophic epithelium (p = 0.042). A larger number of CD57+ NK cells and CD8+ T lymphocytes were observed in grade III infiltrates compared to grade I/II (p = 0.145 and p = 0.725, respectively). CD8+ T lymphocytes were more prevalent than CD57+ NK cells in most cases when PGs and RCs were analyzed separately or in combination (p < 0.0001). CD57+ NK cells and CD8+ T lymphocytes play a key role in antiviral defense and the presence of these cells supports evidence suggesting the participation of these microorganisms in the pathogenesis of PGs and RCs. The response mediated by CD8+ T lymphocytes was more frequent, indicating greater participation of the adaptive immunity in these chronic lesions.

CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT.

We have recently described a specialized subset of human natural killer (NK) cells with a CD56(dim)CD57(+)NKG2C(+) phenotype that expand specifically in response to cytomegalovirus (CMV) reactivation in hematopoietic cell transplant (HCT) recipients and exhibit properties characteristic of adaptive immunity. We hypothesize that these cells mediate relapse protection and improve post-HCT outcomes. In 674 allogeneic HCT recipients, we found that those who reactivated CMV had lower leukemia relapse (26% (17-35%), P=0.05) and superior disease-free survival (DFS) (55% (45-65%) P=0.04) 1 year after reduced intensity conditioning (RIC) compared with CMV seronegative recipients who experienced higher relapse rates (35% (27-43%)) and lower DFS (46% (38-54%)). This protective effect was independent of age and graft-vs-host disease and was not observed in recipients who received myeloablative regimens. Analysis of the reconstituting NK cells demonstrated that CMV reactivation is associated with both higher frequencies and greater absolute numbers of CD56(dim)CD57(+)NKG2C(+) NK cells, particularly after RIC HCT. Furthermore, expansion of these cells at 6 months posttransplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on posttransplant relapse is in part driven by adaptive NK cell responses.

Terminal Differentiation of CD56(dim)CD16(+) Natural Killer Cells Is Associated with Increase in Natural Killer Cell Frequencies After Antiretroviral Treatment in HIV-1 Infection.

HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART.

Aging-associated subpopulations of human CD8+ T-lymphocytes identified by their CD28 and CD57 phenotypes.

BACKGROUND: During organismal aging, human T-cells shift towards less functional phenotypes, often called senescent cells. As these cells have not been well characterized, we aimed to relate surface markers of human T-cell senescence with characteristics of in vitro cellular aging and to further characterize these cells. METHODS: We identified, by flow cytometry, subpopulations of CD8+ T-cells based on CD57 and CD28 expression, and tested them for some markers of cellular senescence, apoptosis, differentiation and homing. RESULTS: Elderly persons presented significantly higher proportions not only of CD28-CD57+, but also of CD28+CD57+ cells. CD28+CD57+ cells had the highest expression of p16, p21, Bcl-2, CD95, CD45RO, CCR5 and PD-1, thereby arguing in favor of a senescent phenotype. CONCLUSION: Among CD8+ T-lymphocytes, CD28+CD57+ cells represent a subset with some senescent features that are distinct from the CD28-CD57+ cells.

A case of a CD56-expressing ectomesenchymal chondromyxoid tumor of the tongue: potential diagnostic usefulness of commonly available CD56 over CD57.

Ectomesenchymal chondromyxoid tumors (ECTs) are rare. Only approximately 55 cases have been reported in the English literature. Distinguishing ECTs from soft tissue myoepithelioma (STM) is often difficult owing to morphological and immunohistochemical similarities. Here, we present a case of an ECT arising from the anterior dorsum of the tongue in a 24-year-old woman. Grossly, the tumor was soft, had a myxoid appearance, and measured 8×7×7 mm. Microscopically, it was well-demarcated, lacked a fibrous capsule, and predominantly consisted of short, spindle to ovoid cells in a myxoid background. Vimentin, glial fibrillary acidic protein (GFAP), and S-100 protein were strongly positive on immunohistochemical analysis. While CD56 was moderately immunopositive, cytokeratin (AE1/AE3) and alpha-smooth muscle actin (αSMA) showed focal weak positivity. Thus, the immunohistochemical findings suggested a diverse immunophenotype, indicating mesenchymal (vimentin and αSMA positive), neurogenic (S100, GFAP, and CD56 positive), and epithelial differentiation (cytokeratin positive). This reflected the fact that ECTs probably arise from uncommitted ectomesenchymal cells that have the potential for multilineage differentiation. The immunohistochemical staining pattern observed for ECTs slightly differs from that of STMs. Strongly positive staining for GFAP and weakly positive staining for cytokeratin are observed in ECTs, whereas the opposite is typically observed for STMs. These findings indicated that the patterns of expression on immunohistochemistry differ between ECTs and STMs, although inevitably, there was some overlap. Thus, CD56 expression in the case presented here is noteworthy, and it could potentially become an adjunct diagnostic marker for ECT instead of previously used CD57.

Aberrant NK cell associated marker (CD56 and CD57) expression in chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is one of the commonest leukemias that has been reported extensively throughout the literature. The characteristic phenotype includes co-expression of CD5 and CD23, along with dim expression of light chain and CD22/CD79b, with lack of FMC7. The immunophenotypic scoring system given by Matutes has been used to differentiate CLL from non-CLL chronic lymphoproliferative disorders. Various aberrancies have been described in CLL cases, including abnormal (dim or bright) expression of B cell markers and lineage infidel T cell, myelomonocytic, or rarely Natural killer (NK) cells markers. However, the aberrant co-expression of CD56 and CD57 has not yet been reported. METHOD AND RESULTS: We hereby report a case of 62-year female with a typical CLL phenotype and Matutes score of 5, showing the expression of CD56 and CD57. CONCLUSION: This entity may represent a rare subtype of CLL which needs to be studied more extensively for its prognostic implications. This is the first report of CLL with aberrant CD56 and CD57 expression.

Chemotherapy-induced changes and immunosenescence of CD8+ T-cells in patients with breast cancer.

BACKGROUND: Changes in sub-populations of cytotoxic (CD8+) T-cells, which are observed in aging and in conditions of chronic immune stimulation, are not well-documented in cancer. MATERIALS AND METHODS: Using flow cytometry, CD8+ T-cell subsets were analyzed in patients with breast cancer undergoing DNA-damaging chemotherapy and in an older female control group during a six-month longitudinal study, to explore shifts in CD8+ T-cells and the effect of DNA-damaging chemotherapy on different T-cell sub-populations. RESULTS: As expected, there was a consistent decrease in absolute numbers of leukocytes, lymphocytes, T-cells and CD8+ T-cells during chemotherapy in patients with cancer. Among the T-cells, there was a lower CD8-/CD8+ ratio, persisting over the six months, in patients with cancer compared to controls. The proportion of CD28-CD57+ cells also remained higher among patients with cancer throughout the sampling duration. The number of CD28+CD57- and CD28-CD5- cells decreased faster during DNA-damaging chemotherapy than CD28+CD57+ and CD28-CD57+ cells, while only CD28-CD57- cells showed a significant reconstitutive capacity after six months. CONCLUSION: Immunosenescence appeared to be pronounced in patients with breast cancer, with senescent CD8+ T-cells playing a role. The normal condition was not restored after six months of chemotherapy.

The immune function differences and high-risk human papillomavirus infection in the progress of cervical cancer.

INVESTIGATION: To study the differences immune function in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical cancer tissue, and study the relationship between human papillomavirus (HPV) infection and cervical local immune function. MATERIALS AND METHODS: This study determined the form, quantity, distribution, and intensity of CD4+Th cells, S-100+ dendritic cells (DCs) and CD57+NK cells in the normal cervical tissue, CIN cervical tissue, and cervical cancer by histopathological and image analyses. RESULTS: The immune function was differences in the progress of cancer genesis. The numbers of the CD4+ Th cells, S-100+ DCs, and CD57+NK cells increased with the progress of the disease in CIN, but when cancer occurred, immune cells decreased in local cervical tissue. CONCLUSION: From lesion precancerous to infiltrating carcinoma, the form, quantity, and intensity of expression of immune cells changed, which may indicate that the cervical local immune function has changed. Furthermore, high-risk HPV infections are more active in local immune function.

Presence of intramucosal neuroglial cells in normal and aganglionic human colon.

The enteric nervous system (ENS) is composed of neural crest-derived neurons (also known as ganglion cells) the cell bodies of which are located in the submucosal and myenteric plexuses of the intestinal wall. Intramucosal ganglion cells are known to exist but are rare and often considered ectopic. Also derived from the neural crest are enteric glial cells that populate the ganglia and the associated nerves, as well as the lamina propria of the intestinal mucosa. In Hirschsprung disease (HSCR), ganglion cells are absent from the distal gut because of a failure of neural crest-derived progenitor cells to complete their rostrocaudal migration during embryogenesis. The fate of intramucosal glial cells in human HSCR is essentially unknown. We demonstrate a network of intramucosal cells that exhibit dendritic morphology typical of neurons and glial cells. These dendritic cells are present throughout the human gut and express Tuj1, S100, glial fibrillary acidic protein, CD56, synaptophysin, and calretinin, consistent with mixed or overlapping neuroglial differentiation. The cells are present in aganglionic colon from patients with HSCR, but with an altered immunophenotype. Coexpression of Tuj1 and HNK1 in this cell population supports a neural crest origin. These findings extend and challenge the current understanding of ENS microanatomy and suggest the existence of an intramucosal population of neural crest-derived cells, present in HSCR, with overlapping immunophenotype of neurons and glia. Intramucosal neuroglial cells have not been previously recognized, and their presence in HSCR poses new questions about ENS development and the pathobiology of HSCR that merit further investigation.