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The risk of postpartum (PP) stroke is increased in complicated pregnancies. Deficiency in CD4 T cell subsets is associated with preeclampsia and may contribute to PP vascular disease, including internal carotid artery (ICA) stenosis and stroke. We hypothesized that CD4 T cell deficiency in pregnancy would result in ICA dysregulation, including enhanced ICA vasoconstriction. We characterized the function, mechanical behavior, and structure of ICAs from C57BL/6 (WT) and CD4 deficient (CD4KO) mice, and assessed the role of NO in the control of ICA function at pre-conception and PP. WT and CD4KO mice were housed under pathogen-free conditions, mated to same-strain males, and allowed to litter or left virgin. At 3 days or 4 weeks PP, mice were euthanized. The responses to phenylephrine (PE), high K+ and acetylcholine (ACh) were assessed in pressurized ICAs before and after NOS inhibition. Passive lumen diameters were measured at 3–140 mmHg. eNOS and iNOS expression as well as the presence of T cells were evaluated by immunohistochemistry. Constriction of WT ICAs to PE was not modified PP. In contrast, responses to PE were significantly increased in ICAs from PP as compared to virgin CD4KO mice. Constriction to high K+ was not enhanced PP. ICAs from WT and CD4KO mice were equally sensitive to ACh with a significant rightward shift of dose-response curves after L-NNA treatment. NOS inhibition enhanced PE constriction of ICAs from WT virgin and PP mice. Although a similar effect was detected in ICAs of virgin CD4KO mice, no such changes were observed in vessels from PP CD4KO mice. Passive arterial distensibility at physiological levels of pressure was not modified at PP. ICA diameters were significantly increased in PP with no change in vascular wall thickness. Comparison of eNOS expression in virgin, 3 days and 4 weeks PP revealed a reduced expression in ICA from CD4 KO vs. WT PP vessels which reached significance at 4 weeks PP. iNos expression was similar and decreased over the PP period in vessels from WT and CD4KO mice. Dysregulation of the CD4 T cell population in pregnancy may make ICA vulnerable to vasospasm due to decreased NO-dependent control of ICA constriction. This may lead to cerebral hypoperfusion and increase the risk of maternal PP stroke. [ABSTRACT FROM AUTHOR]

Summary: Background: The immunopathogenesis of severe asthma has been associated with an inefficient regulatory response. There are a few studies about the CD4 T cells profile among individuals with severe asthma refractory to treatment. Objective: To evaluate the CD4 T lymphocyte profile from individuals with severe asthma according to their response to treatment, relating to their atopy status and age of asthma onset. Methods: We evaluated nineteen individuals with severe asthma refractory to treatment (SAR), 21 with well‐controlled or partly controlled severe asthma (CSA) and 23 with mild‐to‐moderate asthma (MMA). Lymphocytes were obtained from PBMC, and the frequency of expression of different molecules in this population was assessed using the flow cytometry. Results: We observed the frequency of CD4+IFN‐γ+T cells was higher in atopic individuals with SAR than with CSA. In addition, among the atopic and early‐onset asthma (EOA), the frequency of CD4+CTLA‐4+T cells was lower in the SAR group than the CSA group. In relation to non‐atopic and late‐onset asthma (LOA) phenotypes, we noted the frequency of CD4+FoxP3+T cells was lower in individuals with SAR than with CSA. We also observed among the LOA patients, the frequency of CD4+TGF‐β+ T cells was decreased in SAR group than the in CSA group. Conclusion and Clinical Relevance: Our data suggest that refractoriness to treatment in asthma is associated with a lower expression of distinct regulatory molecules by CD4 T cells between those who are atopic and have EOA and those who are non‐atopic and have LOA. Thus, these results may contribute to the identification of new regulatory strategies to treat asthma according to their phenotypes. [ABSTRACT FROM AUTHOR]

Objective: Herpes simplex virus 1 (HSV-1) is regarded as an important underlying cause of Bell's palsy, but the immunologic mechanism remains unknown. Here, we employed a mouse facial paralysis model to investigate the expressions of CD4 T lymphocytes and interleukin (IL)-2 and -4 in the left draining cervical lymph nodes (LCLN) and spleen, as well as the inhibitory effects of glucocorticoids (GCs). Methods: HSV-1 was inoculated into the surface of the posterior auricle to generate the facial paralysis model. The paralyzed mice were divided into three groups; in one group without any treatment, mice were killed at different time points, and those in the other two groups were injected with methylprednisolone sodium succinate (MPSS) or with a combination of MPSS and GC receptor blocker (RU486). The expression levels of CD4 T lymphocytes and CD4-IL-2 and CD4-IL-4 cells in the LCLN and spleen were detected by fluorescence-activated cell sorting. Results: Expression levels of CD4, IL-2, and IL-4 first increased then decreased in LCLN and spleen and peaked 5 and 7 days, respectively, after the manifestation of facial paralysis. All the data at the peak points were significantly different compared with control ( p < 0.05), and these effects were inhibited by MPSS. Conclusion : Our results suggest that CD4, IL-2, and IL-4 participate in the HSV-1-induced facial paralysis immune response. MPSS can effectively attenuate HSV-1-mediated nervous system damage, which is associated with its inhibitory effect on expression of these inflammatory markers. [ABSTRACT FROM AUTHOR]

Abstract: Reactivity of lamina propria (LP) T cells to commensal bacteria has been demonstrated in animal models of inflammatory bowel disease (IBD) and in humans with IBD, but few studies have evaluated the function of such cells in normal individuals. LP mononuclear cells (LPMC) were disaggregated from healthy human intestinal tissue and cultured with heat-killed commensal and pathogenic bacteria. CD3+CD4+ IFN-γ-producing (Th1) cells reactive to commensal bacteria were demonstrated at frequencies ranging from 0.05 to 2.28% in LPMC. Bacteria-specific Th1 responses were inhibited by anti-HLA-DR antibodies and chloroquine exposure, were enriched in LP relative to peripheral blood, and expressed effector memory cell markers. Bacteria-specific CD4+ T cell proliferation in vitro was dependent on the presence of LP dendritic cells (DCs), which produced pro-inflammatory cytokines upon bacterial exposure. These results suggest that bacteria-reactive DCs and CD4+ T cells in normal LP have substantial pro-inflammatory potential that is revealed upon disaggregation in vitro. [Copyright &y& Elsevier]

Background: In the context of scaling the viral load in resource limited settings, following HIV infected patient's adults and children with CD4+ T-lymphocyte count still very important in settings where the decentralization of treatment still has some challenges. Effective HIV monitoring in these resource-constrained settings needs affordable and reliable CD4+ T lymphocytes enumeration methods. We investigated the validity of a BD FACSPresto POC which is a dedicated system for enumeration that uses immunofluorescent technologies. In this study, we have assessed the sensitivity, specificity and correlation between most representative flow cytometry instruments present in Cameroon with more than 5000 CD4 T cells tests per year including FACSCalibur, FACSCount, and PIMA POC from Becton–Dickinson and ALERE respectively. Methods: 268 patients aged from 1 to 72 years old were enrolled and included in the study after inform consent. The BD FACSPresto POC CD4+ T cell technology was placed at CIRCB and operated by technician staff. HIV infected patients were from Chantal BIYA international reference Center (CIRCB), Centre de Sante Catholique de NKOLODOM, Centre de Sante Catholique de BIKOP and CASS de Nkolndongo—Yaounde We compared the accuracy of the BD FACSPresto and three existing reference technologies with more than 5000 tests per year like FACSCalibur, FACSCount and PIMA according to the number of CD4 test done per year and their repartition in the country. Bland–Altman method and correlation analysis were used to estimate mean bias and 95% limits of agreement and to compare the methods, including analysis by subgroup of participant gestational age. In addition sensitivity and specificity were determined. Statistical significance was set at P-value < 0.05. Results: The BD FACSPresto POC system has excellent precision, accuracy and linearity for CD4+ T lymphocytes enumeration. Good correlations were obtained between the BD FACSPresto poc system and other single platform methods. Bland–Altman plots showed interchangeability between two machines mean bias BD-FACSPresto vs PIMA = − 126,522(− 161,221 to − 91,822) BD-FACSPresto vs FACSCount = − 38,708 (− 58,935 to − 18,482) and FACSPresto vs FACSCALIBUR = 0.791(− 11,908 to 13,491). Mean difference with Absolute CD4+ T-lymphocyte values obtained from the BD FACSPresto system correlated well with PIMA, FACSCount, and FACSCalibur method with R2 equal to 0.88, 0.92 and 0.968 respectively with P < 0.001 for all. The mean comparison between values obtained from BD FACSPresto with PIMA, FACSCount, and FACSCalibur using paired T test give P = 0.17, P = 0.5 and P = 0.6 respectively meaning that there is no significant differences between values obtained with BD FACSPresto and PIMA, FACSCount or FACSCalibur CD4 enumeration machines. Further analysis revealed close agreement between all the three instruments with no significant difference between the forth methods (P = 0.91). Conclusion: This BD-FACSPresto POC system is a simple, robust and reliable system for enumeration of absolute and percentage of CD4+ T-lymphocytes especially suitable for remote areas with limited resources. Having one BD-FACSPresto POC system easy to use, should reduce the cost and thus increase and improved access to CD4 testing for HIV infected patients in resource-constrained countries. BD-FACSPresto POC CD4 will enable reduction in patient time and improve the overall quality of ART service count and may improve test access in remote areas. This technology can allow for greater decentralization and wider access to CD4 testing and ART. [ABSTRACT FROM AUTHOR]