Heterogeneous trajectories of CD4 T cells in aging: Implications to the biology of aging and age-related disease susceptibility

Age-associated changes in the structure and functionality of CD4 T-cell subsets have been linked to declined immunity, chronic inflammation, and increased risk for cancer and neurodegenerative diseases. However, characterization of the detailed transcriptional diversity of CD4 T-cell subsets in human aging is yet not fully explored. Our recent single cell RNA sequencing (scRNA-seq) results from young and old mice showed the accumulation of two new age-related populations; cytotoxic CD4 T cells (CTLs) and activated Tregs (aTregs) which exhibit extreme inflammatory and regulatory function, respectively. Here, we will apply 10X chromium scRNA-seq to CD4 T cells from young and old healthy individuals. By using computational analysis, we identify the landscape and population structure of CD4 T cells in each age group. To date, we screened ~60,000 CD4 T cells from 4 young and 4 old individuals, showing age-related differences in cell subsets and their frequencies. Moreover, we validated the accumulation of age-related subsets with flow cytometry. The heterogeneous trajectories of CD4 T cells in aging will be discussed in the context of metabolic dysfunction, the biology of aging and age-related disease susceptibility.

*Equal contribution