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

In adults, a majority of FOXP3(+) T-regs 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(+) T-regs 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(+) T-regs within the CD4(+)CD25(+) T cell population and the fractions of CD4(+) T cells that expressed CD45RA, CD45RO, HLA-DR, alpha(4)beta(7), 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(+) T-regs during the first 18 months of life was associated positively with the fraction of T cells that expressed a naive phenotype (CD45RA and alpha(4)beta(7)) 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(+) T-regs may modulate CD4(+) T cell activation and homing receptor expression in children. J. Leukoc. Biol. 90: 1133-1140; 2011.