Anti-CD4 monoclonal antibody, clone DE5-I3

In early equine pregnancy, a highly invasive trophoblast cell subpopulation, the chorionic girdle cells, invade the endometrium and form endometrial cups (EC). These cells express classical MHC molecules, thereby stimulating a humoral and cellular immune response, resulting in a massive accumulation of maternal CD4+ and CD8+ T cells around the EC. Nevertheless, no immediate destruction of endometrial cups by maternal lymphoid cells occurs, presumably due to immune tolerance. Although the environment of EC is rich in TGFB and in FOXP3+, CD4+ T cells, the mechanisms leading to tolerance have not been elucidated. Recently, we discovered that equine trophoblast cells secrete pregnancy-specific glycoproteins (PSGs). Since human and murine PSGs activate latent TGFB, we hypothesized that equine PSGs may have a similar activity. We performed plasmon surface resonance experiments to show that equine PSG CEACAM49 can directly bind to the latency-associated peptide (LAP) of both TGFB1 and TGFB2. We then found that the binding of CEACAM49 leads to the activation of TGFB1 as determined by both ELBA and cell-based assays. Furthermore, the activation of TGFB is a unique function of PSGs within the human CEA family, because CEACAMI, 3, 5, 6, 8 do not activate this cytokine. This finding further strengthens the classification of CEACAM49 as an equine PSG. Based on our results, we hypothesize that activation of latent TGFB in the EC environment by equine PSGs secreted by invasive trophoblast cells, could contribute to the generation of regulatory T cells (Tregs) to maintain immune tolerance.

Background: Little is known about hospitalization in African adolescents with perinatally acquired HIV (PHIV+ adolescents). We described the incidence and causes of hospitalization in participants enrolled in the Cape Town Adolescent Antiretroviral Cohort in South Africa. Methods: Data collected from July 2013 to October 2018 from PHIV+ and HIV- adolescents were analyzed. Participants were assessed every 6 months and data on intercurrent hospitalization were abstracted. Causes of hospitalizations were classified according to ICD-10 codes. Descriptive statistics, time-to-event analysis and Poisson regression were used to describe causes and incidence and to determine incidence rate ratios for factors associated with hospitalization. Results: Five hundred fifteen PHIV+ and 109 HIV- participants had a median follow-up of 4.1 years [interquartile range (IQR): 3.7-4.6]. At enrollment HIV+ participants had a median duration of ART of 7.6 years (IQR: 4.6-9.2), median CD4 count of 713 cells/mm(3)(IQR: 561.0-957.5) and 387 (75%) had a viral load <50 copies/mL. There were 149 hospital admissions over 64 months. Crude incidence rates for hospitalization were 6.6 [95% confidence interval (CI): 5.7-7.8] and 2.2 (95% CI: 1.2-4.3) per 100-person-years (P= <0.01) in HIV + and HIV-, respectively. Ninety of 149 (60%) admissions in HIV+ participants were classified as non-infectious, 36/149 (24%) were infectious and 23/149 (16%) were "other HIV-related" or "unknown." Older age (15-19 years) and maintaining a CD4 >500 cells/cm(3)were associated with decreased risk of hospitalization: adjusted incidence rate ratios of 0.61 (CI: 0.44-0.86,P= <0.01) and 0.68 (CI: 0.49-0.94,P= 0.02), respectively. Conclusions: PHIV+ adolescents had a high incidence of hospitalization despite ART. Strategies addressing infectious and non-infectious morbidity must be strengthened.