Anergy is a Survival Advantage for the Maintenance of Memory CD4+ T Cells (36.10)

Abstract

Abstract The hallmarks of specific T cell immunity include proliferative expansion, and acquisition of effector function. The outcome is resolution of the infection and the generation of memory T cells (Tmem). Although majority of Tmem cells die following clearance of infection, a fraction survives through lifetime and is protective on recall. It is not clear how Tmem decline with the fall of antigenic load and survive so long in the absence of antigen. Using CpG mixed with antigen to mimic an infection, we have shown that CD4+ Tmem cells undergo anergy upon encountering suboptimal doses of antigen, a condition that associates with the fall of antigenic load expected post resolution of an infection. We demonstrate that follicular B (B2) cells, and not DCs, induce anergy in CD4+ Tmem by upregulating CTLA-4 expression. These findings suggest that B cells bearing high affinity antigen receptor regulate responsiveness of Tmem by capturing the lowest levels of antigen likely present after the clearance of an infection, and signal Tmem to undergo anergy. We also show that the anergized cells are activated by stimulatory signals generated by innate immunity at the onset of a subsequent infection. Our study suggest that anergy is a mechanism to regulate long-term survival of Tmem in the absence of antigen by preventing unnecessary proliferations that lead to death. Supported by R01GM53549 and R01AI063764 grants to SS-N.