Memory cells derived from homeostatic proliferation defer to true memory during infection

Abstract

In the absence of antigen, CD8+ T cells derived from lymphopenia induced homeostatic proliferation (HP) acquire many phenotypic markers and functional characteristics typical of true memory CD8+ T cells. To understand better the basis of competition in the memory compartment, we explored the differences between these two populations. We performed a mixed adoptive transfer of HP memory‐like T cells and true memory CD8+ OT‐I T cells into the same recipient, followed by infection with L. monocytogenes expressing ovalbulmin. In the context of the mixed transfer, we observed differences that were not apparent in single transfers of each cell type alone. When in competition with one another, we found that the HP memory‐like T cells underwent reduced expansion and failed to form an equivalent amount of secondary memory compared to the true memory CD8+. The HP memory‐like T cells also preferentially localized to the lymph nodes, while the population of true memory T cells dominated in all the other tissues, including the spleen, lung, liver, and bone marrow. These results point to the existence of previously unknown differences between HP memory‐like and true memory CD8+ T cells arising in the context of competition. Future experiments will focus on elucidating the nature of the defective immune response by the HP memory‐like CD8+T cells.