Memory-like CD8+ T cells generated during homeostatic proliferation defer to antigen-experienced memory cells

Naive T cells proliferate in response to lymphopenia and acquire the phenotypic and functional qualities of memory T cells, providing enhanced protection against infection. How well memory-like T cells generated during lymphopenia-induced homeostatic proliferation (HP)-memory differentiate into secondary memory cells and compete with Ag-experienced true-memory cells is unknown. We found that CD8(+) HP-memory T cells generated robust responses upon infection and produced a secondary memory population comparable to true-memory cells in the absence of competition. However, when true-memory and HP-memory T cells competed during infection, HP-memory cells contributed less to the effector population, contracted earlier, and formed fewer secondary memory cells. Furthermore, HP- and true-memory cells demonstrated distinct chemokine receptor expression and localization within the spleen during infection, indicating differential access to signals necessary for secondary memory formation. Thus, HP-memory T cells provide protection without compromising the true-memory population. Differences in HP- and true-memory T cells may reveal the basis of competition for limited resources within the memory-T cell compartment.