Age-related alterations in human gut CD4 T cell phenotype, T helper cell frequencies, and functional responses to enteric bacteria

Intestinal lamina propria (LP) CD4 T cells play critical roles in maintaining intestinal homeostasis and in immune responses to enteric microbes, yet little is known regarding whether they contribute to age-associated intestinal immune dysfunction. In this study, we evaluated the direct ex vivo frequency, activation/inhibitory phenotype, death profiles, and in vitro functional responses of human jejunum LP CD4 T cells, including Th1, Th17, and Th22 subsets isolated from younger (<45 years) and older (>65years) persons. Expression of the co-inhibitory molecule CTLA-4 was significantly lower in older CD4 T cells, whereas expression of HLA-DR, CD38, CD57, and PD-1 were not significantly different between groups. Total CD4 T cell frequencies were similar between age groups, but lower frequencies and numbers of Th17 cells were observed directly ex vivo in older samples. Older Th17 and Th1 cells proliferated to a lesser degree following in vitro exposure to bacterial antigens vs. their younger counterparts. Levels of spontaneous cell death were increased in older CD4 T cells; however, cellular death profiles following activation did not differ based on age. Thus, small intestinal CD4 T cells from older persons have altered phenotypic and functional profiles including reduced expression of a co-inhibitory molecule, increased spontaneous cell death, and both reduced frequencies and altered functional responses of specific Th cell subsets. These changes may contribute to altered intestinal homeostasis and loss of protective gut immunity with aging.