Inhibitory effects of transforming growth factor-beta (TGF-β) on certain functions of intraepithelial lymphocytes

Human intraepithelial lymphocytes (IEL), CD8+ lymphocytes located between epithelial cells, are likely to be influenced by the immunosuppressive cytokine, TGF-β, secreted by epithelial cells. This study evaluates the effects of TGF-β on IEL functions. IEL were derived from proximal jejunum of patients undergoing gastric bypass operations for morbid obesity. Proliferation was determined by 3H-thymidine incorporation; IL-2 production, by ELISA; expression of IL-2 receptor, CD2, HML1, CD16, and CD56, by immunofluorescence; binding, by adherence of radiolabelled cells; and cytotoxicity by 51Cr-release assay. TGF-β (≥ 1 ng/ml) inhibited the mitosis of IEL to mitogens, IL-7, and stimuli of the CD2 and CD3 pathways. The blocking effect did not target the activation events of IL-2 production and receptor generation. Rather, it reduced cell division after activation when added 24 h after initiating the culture. Antibody neutralization of naturally occurring TGF-β increased IEL proliferation to IL-2, but not to the other stimuli. Of the multiple surface markers tested, only CD2 and HML1 expression increased with TGF-β and decreased with antibody to TGF-β, although the cytokine and the neutralizing antibody had no effects on IEL binding to colon cancer. TGF-β reduced the number of CD56+ IEL and the lymphokine-activated killing when co-cultured with IL-7 but not with IL-2 or IL-15. TGF-β inhibits certain IEL functions: the reduction in cell division rather than activation and a decline in IL-7-mediated lysis of colon cancer due to a lowering of the number of natural killer cells

Increased Risk of HIV Acquisition Among Women Throughout Pregnancy and During the Postpartum Period: A Prospective Per-Coital-Act Analysis Among Women With HIV-Infected Partners

BackgroundUnderstanding the absolute and relative risk of human immunodeficiency virus type 1 (HIV) acquisition during pregnancy and the postpartum period can inform HIV prevention strategies for women.MethodsWe used a complementary log-log model and data from 2751 HIV-serodiscordant couples to compare the probability of HIV acquisition among women per sex act during early pregnancy, late pregnancy, the postpartum period, and the nonpregnant period.ResultsAt total of 686 pregnancies were identified, and 82 incident HIV infections occurred. After adjustment for condom use, age, preexposure prophylaxis (PrEP) use, and HIV viral load, the per-act probability of HIV acquisition was higher in late pregnancy (adjusted relative risk [aRR], 2.82; P = .01) and the postpartum period (aRR, 3.97; P = .01) as compared to that during nonpregnant period. For a 25-year-old woman not taking PrEP, the HIV acquisition probability per condomless sex act with an HIV-infected male partner with a viral load of 10 000 copies/mL was 0.0011 (95% confidence interval [CI] 0.005-0.0019), 0.0022 (95% CI, 0.0004-0.0093), 0.0030 (95% CI, 0.0007-0.0108), and 0.0042 (95% CI, 0.0007-0.0177) during the nonpregnant period, early pregnancy, late pregnancy, and the postpartum period, respectively.ConclusionThe HIV acquisition probability per condomless sex act steadily increased during pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and the postpartum period increase HIV susceptibility among women