Intestinal double positive CD4+CD8+ T cells of neonates are highly activated memory cells with higher proliferative capacity compared to single positive CD4+/CD8+ T cells (B115)

Abstract

Abstract Peripheral blood and thymic double positive CD4+CD8+ (DP) T cells from neonates have been described in humans and a number of animals, but the function and immunophenotypic characteristics of other tissue-derived DP T cells are not clearly understood. Here we demonstrate the phenotypic characteristics of DP cells in 6 different tissues including thymus from normal neonatal rhesus macaques (Macaca mulatta) between 0–21 days of age. In general, DP T cells of neonates have higher percentages of memory markers (CD28+CD95+, CD45RA−) compared to single positive (SP) CD4+ and CD8+ T cells. In addition, intestinal DP T cells increase as the animals’ age and levels of CD62L decrease with age suggesting that DP cells proliferate and are activated with maturity and/or antigen exposure. Consistent with this, intestinal DP T cells in neonates express higher levels of activation markers and CCR5 expression. Furthermore, DP T cells have higher rates of proliferation compared to SP CD4+ and SP CD8+ T cells as determined by BrdU labelling techniques. Finally, DP T cells produce higher levels of cytokine production in response to mitogen stimulation compared to SP CD4+ or SP CD8+ T cells. Collectively, these findings demonstrate that intestinal DP T cells of neonates are proliferating, effector cells and are likely involved in regulating immune as compared to the immature DP T cells in the thymus. As in adults, these intestinal DP T cells may be important target cells for early HIV infection in neonates due to their activation, high expression of CCR5, and memory phenotype.