A follicular regulatory Innate Lymphoid Cell population impairs interactions between germinal center Tfh and B cells

Innate Lymphoid Cells (ILCs) are immune cells typically found on mucosal surfaces and in secondary lymphoid organs where they regulate the immune response to pathogens. Despite their key role in the immune response, there are still fundamental gaps in our understanding of ILCs. Here we report a human ILC population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILCFR) that to our knowledge has not been previously identified. ILCFR have a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILCFR inhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILCFR to the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-β. Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILCFR in regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.

Differential sensitivity of myeloid and lymphoid cell populations to apoptosis in peritoneal cavity of mice with model larval Mesocestoides vogae infection

SummaryThe metacestode stage of the tapeworm Mesocestoides vogae (M. vogae) has the ability of asexual growth in the peritoneal cavity of rodents and other intermediate hosts without restriction. Early immunological events have decisive role in the establishment of infection. In the present study we investigated the kinetic of myeloid and lymphoid cell populations and the proportions of cells undergoing apoptosis in peritoneal cavities of mice within the first month after oral infection with M. vogae larvae. Proportions of cell phenotypes and apoptotic cells were examined by flow cytometry and by microscopical analysis of cells following May/Grünwald staining and fluorescent stain Hoechst 33234, respectively. Total numbers of peritoneal cells increased and their distribution changed towards accumulation of myelo-monocytic cell lineage in the account of reduced proportions of lymphoid cells. CD4+ T cell subpopulations were more abundant than CD8+ and their proportions elevated within two weeks post infection (p.i.) which was followed by a significant decline. Expression level of CD11c marker on myelo-monocytic cells revealed phenotype heterogeneity and proportions of cells with low and medium expression elevated from day 14 p.i. along with concurrent very low presence of CD11chigh phenotype. Lymphoid cell population was highly resistant to apoptosis but elevated proportions of myeloid cells were in early/late stage of apoptosis. Apoptosis was detected in a higher number of adherent cells from day 14 p.i. onwards as evidenced by nuclear fluorescent staining. By contrast, cells adherent to larvae, mostly macrophages and eosinophils, did not have fragmented nuclei. Our data demonstrated that apoptosis did not account for diminished population of peritoneal lymphoid cells and substantial proportions of myeloid cells seem to be more susceptible to apoptotic turnover in peritoneal cavity of mice with ongoing M. vogae infection, suggesting their important role in the host-parasite interactions.

CYTOMORPHOLOGICAL DETECTION OF MALIGNANT EFFUSIONS IN NON-HODGKIN LYMPHOMA: AN INSTITUTIONAL EXPERIENCE IN A DEVELOPING COUNTRY

Objective: Lymphomatous effusions of the body cavity may be the presenting feature or develop later as a complication of systemic disease. The detection rate of lymphoma in cytologic specimen is low, especially in the absence of clinical details and ancillary studies. The present study was carried out to identify light microscopic features that are useful in identifying lymphomas on effusion cytology. Methods: A 5-year retrospective study of all patients with fluid cytology or tissue biopsy reported as suspicious or positive for non-Hodgkin lymphoma (NHL) in a tertiary care was done. The cytology, histopathology, and immunohistochemistry slides were reviewed. Results: A total of 27 cases were included in the study. Correlation with the histopathological sections of all the positive cases revealed that the cytomorphology of the abnormal lymphoid cells was monomorphous and similar to those seen in the tissue biopsy. Mercury drop karyorrhexis when present was characteristic of lymphomatous effusions. The detection rates of large cell lymphomas are higher than low-grade counterparts. Non-lymphomatous effusions showed heterogeneous lymphoid cell population and lacked karyorrhexis. Conclusion: Lymphomas can give rise to effusions. In the absence of resources in developing countries, it is important to distinguish lymphomatous effusion from a reactive process based on morphology. Monomorphous population of the lymphoid cells and presence of mercury drop karyorrhexis are useful morphological clues in identifying a lymphomatous effusion. Further, tuberculosis is a common non-neoplastic process that can be mistaken for a low-grade NHL.

Lamivudine-Induced Liver Injury

BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention.AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine.MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10–day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ–glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S–transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05.RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100 mg/kg.CONCLUSION: Lamivudine toxicity in rat liver appeared to be mediated by oxidative stress.

Parathyroid Adenoma with Prominent Lymphocytic Infiltrate

Only very few previously reported cases of pronounced lymphocytic infiltration in parathyroid adenoma can be found in the English medical literature. The objective of this report is to present such a rare case and to investigate to a certain extent the immunohistochemical profile of this rare histologic observation. The lymphoid cell population within the tumour was composed of nodule-forming B-cells and different subsets of infiltrating T-cells and caused minimal destruction of neoplastic tissue.