Higher proportions of circulating FOXP3+ and CTLA-4+ regulatory T cells are associated with lower fractions of memory CD4+ T cells in infants

Abstract

In adults, a majority of FOXP3+ Tregs expresses CTLA-4, and this costimulatory molecule is essential to control the expansion of other T cells. However, it remains to be investigated whether FOXP3+ and/or CTLA-4+ Tregs are associated with the expression of memory markers and homing receptors on CD4+ T cells. Thus, in a prospective newborn-infant cohort study, we examined the proportions of FOXP3+ and CTLA-4+ Tregs within the CD4+CD25+ T cell population and the fractions of CD4+ T cells that expressed CD45RA, CD45RO, HLA-DR, α4β7, CD62L, and CCR4 at several time-points during the first 3 years of life using flow cytometry. With the use of multivariate factor analysis, we found that a high proportion of FOXP3+ or CTLA-4+ Tregs during the first 18 months of life was associated positively with the fraction of T cells that expressed a naïve phenotype (CD45RA and α4β7) and inversely related to the fraction of T cells that expressed a memory phenotype (CD45RO and CCR4) later in childhood. In conclusion, FOXP3+ or CTLA-4+ Tregs may modulate CD4+ T cell activation and homing receptor expression in children.