Sex Disparity in Cord Blood FoxP3+ CD4 T Regulatory Cells in Infants Exposed to Malaria In Utero

Mary Prahl, Prasanna Jagannathan, Tara I McIntyre, Ann Auma, Samuel Wamala, Mayimuna Nalubega, Kenneth Musinguzi, Kate Naluwu, Esther Sikyoma, Rachel Budker, Pamela Odorizzi, Abel Kakuru, Diane V Havlir, Moses R Kamya, Grant Dorsey, Margaret E Feeney, Mary Prahl, Prasanna Jagannathan, Tara I McIntyre, Ann Auma, Samuel Wamala, Mayimuna Nalubega, Kenneth Musinguzi, Kate Naluwu, Esther Sikyoma, Rachel Budker, Pamela Odorizzi, Abel Kakuru, Diane V Havlir, Moses R Kamya, Grant Dorsey, Margaret E Feeney

Abstract

Sex differences in the immune response and in infectious disease susceptibility have been well described, although the mechanisms underlying these differences remain incompletely understood. We evaluated the frequency of cord blood CD4 T cell subsets in a highly malaria-exposed birth cohort of mother-infant pairs in Uganda by sex. We found that frequencies of cord blood regulatory T cell ([Treg] CD4+CD25+FoxP3+CD127lo/-) differed by infant sex, with significantly lower frequencies of Tregs in female than in male neonates (P = .006). When stratified by in utero malaria exposure status, this difference was observed in the exposed, but not in the unexposed infants.

Keywords: T regulatory cells; immunity; malaria; sex; vaccines..

Figures

Figure 1.
Figure 1.
Lower frequency of cord blood T regulatory cells (Tregs) in females vs males in in utero malaria-exposed infants. (A) Cord blood cells were gated on live, single lymphocytes, dump-negative T cells. Gating of CD4+CD25+ cord blood T cells revealed 2 distinct subsets, Tregs (CD25+FoxP3+CD127lo/−) and activated CD4 T cells (CD25+FoxP3−CD127hi). (B) The frequency of cord blood Tregs (CD25+FoxP3+CD127lo/−) from all infants evaluated, regardless of in utero malaria exposure, differs by sex (P = .006; Wilcoxon rank-sum testing; error bars indicate median with interquartile range; n = 166). (C) The frequency of Tregs differs by sex in the in utero malaria-exposed infants (P = .012), but not the malaria-unexposed infants (P = .353; Wilcoxon rank-sum testing; error bars indicate median with interquartile range).

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