Obesity impairs cell-mediated immunity during the second trimester of pregnancy.

OBJECTIVE: Obese pregnancy is associated with significantly higher rates of infection, which can harm both mother and fetus. The objective of this study was to determine the impact of obesity on maternal blood immune function. STUDY DESIGN: This was a cross-sectional, case control study of 15 obese (Ob) and 15 lean (Lc) subjects. Immune cell subsets, intracellular and serum cytokine production, and lymphocyte proliferation were measured in maternal blood during the second trimester of pregnancy. RESULTS: Obese women had a significantly lower proportion of CD8+ and NKT cells and a higher proportion of B cells, impaired cytokine production when stimulated ex vivo, and impaired ability of lymphocytes to proliferate compared with their lean counterparts. CONCLUSION: Obese pregnancy is associated with impaired cell-mediated immunity. Because perinatal infections can have serious maternal and fetal consequences, it is imperative to better understand these mechanistic underpinnings to optimize prevention and devise targeted therapy.

Inducible costimulator controls migration of T cells to the lungs via down-regulation of CCR7 and CD62L.

We and others reported that inducible costimulator-deficient (ICOS(-/-)) mice manifest a defect in Th2-mediated airway inflammation, which was attributed to reduced Th2 differentiation in the absence of ICOS signaling. Interestingly, the number of CD4 T cells present in the airways and lungs after sensitization and challenge is significantly reduced in ICOS(-/-) mice. We now show that this reduction is not attributable simply to a reduced proliferation of ICOS(-/-) cells, because significantly more ICOS(-/-) than wild-type activated CD4 T cells are present in the lymph nodes, suggesting that more ICOS(-/-) CD4 T cells than wild-type CD4 T cells migrated into the lymph nodes. Further investigation revealed that activated ICOS(-/-) CD4 T cells express higher concentrations of the lymph node homing receptors, CCR7 and CD62L, than do wild-type CD4 T cells, leading to a preferential return of ICOS(-/-) cells to the nondraining lymph nodes rather than the lungs. Blocking reentry into the lymph nodes after the initiation of Th2-mediated airway inflammation equalized the levels of CD4 and granulocyte infiltration in the lungs of wild-type and ICOS(-/-) mice. Our results demonstrate that in wild-type CD4 T cells, co-stimulation with ICOS promotes the down-regulation of CCR7 and CD62L after activation, leading to a reduced return of activated CD4 T cells to the lymph nodes and a more efficient entry into the lungs.