Age-related changes in the immune phenotype of human memory CD4 T cells differ between colon and peripheral blood

Gut lamina propria (LP) CD4 T cells are primarily tissue resident memory cells that are critical in maintaining gut homeostasis and responding to enteric pathogens. We established that aging altered the phenotypic and functional profiles of human small intestinal CD4 T cells. However, given site-specific differences in immune cell composition in the gut, it is difficult to extrapolate these findings to other locations. To probe the effect of aging on large intestine CD4 T cells, we used flow cytometry to analyze immune phenotypes of colon LP CD4 T cells from younger (34±2yrs mean±SEM; N=6) and older (80±2yrs, N=6) adults. Tissue-specificity of these profiles was determined by comparing to memory (CD45RA−) peripheral blood (mPB) CD4 T cells in a separate cohort of similarly aged persons (N=6/age group). Among younger samples, LP CD4 T cells expressed higher levels of co-inhibitory molecules CTLA4 and PD1, but had lower turnover (Ki67+) and IL2 receptor (CD25) expression relative to mPB CD4 T cells. Expression of activation (CD38, HLA-DR), senescence (CD57) and survival (Bcl2) markers were similar. Regarding age effects, frequencies of LP CD4 T cells (% of CD3 T cells) were similar between older and younger samples; mPB CD4 T cell frequencies were higher in older vs younger samples. Older LP CD4 T cells had lower CTLA4, PD1, CD38, CD25 and Ki67 and higher Bcl2 expression than younger LP CD4 T cells. Among mPB CD4 T cells, greater age was only associated with a higher CD57+ fraction. Thus, age effects differed between colon LP and mPB CD4 memory T cells. Loss of co-inhibitory markers, decreased turnover and increased survival of colon LP CD4 T cells may contribute to altered homeostasis, loss of protective immunity, and chronic inflammation in older people.