Olga Britanova
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russia
Title: T cell immunosenescence and longevity
Biography
Biography: Olga Britanova
Abstract
The immunosenescence alterations in the T cell immunity contribute to deficiencies in response to vaccination, in protecting from various infections and increases risk of cancer development and autoimmune diseases. One of the hallmarks of age-related processes is shrinking diversity of TCR repertoire which, on the cellular level, is associated with loss of naïve T cells and expansion of the memory and effector T cell populations. Implementing quantitative TCR repertoire profiling, we investigated changes in diversity and architecture of human TCR repertoires starting from umbilical cord blood to centenarian blood samples. Besides the overall reduction in the TCR repertoire diversity with age, we found that TCR diversity and percentage of naive CD4+ cells in males decreases significantly faster by the age of 40 compared to females. This gender difference disappears in more elderly individuals. Remarkably, percentage of naive T cells within CD4 pool stably decreases with age but remains unexpectedly high in the oldest cohort (>75 y.o.) comparing to the ratio in CD8+ compartment. It might indicate a possible association between high percentage of naive CD4+ cells and longevity. Despite the fact that naive CD4+ cells have low survival capacity than naive CD8+, the homeostatic machinery maintains naive CD4+ pool diverse with age. Additionally, our analysis showed that functional TCR repertoires are more similar in the youth, and this similarity gradually decreased with age. These phenomena might be explained by enrichment of public clonotypes among naive T cells, including clones that originate from fetal period. Further analysis of sorted naive CD8 TCR repertoires across different age groups revealed that naive CD8 repertoires were more similar among young compared to aged donors. Identification of mechanisms driving ageing of TCR repertoire might shed light on vulnerability of elderly to infections, autoimmune disease and cancer development.