UC San Diego

Different subsets of memory CD8⁺ T cells populate the T cell compartment. Antigen-experienced memory (true-memory) cells are formed in a classic immune response against an invading pathogen, but memory-like (HP-memory) cells can also be generated through antigen-independent homeostatic proliferation resulting from lymphopenia. HP-memory cells subsequently acquire the same effector functions and surface marker expression as true-memory cells. When HP- and true-memory CD8⁺ cells of the same specificity compete in conditions of infection, true-memory cells expand to a greater degree and form more secondary memory. Here, we found that HP- and true-memory cells demonstrated aberrant chemokine receptor expression and distinct localization within the spleen during infection, indicating differential access to signals necessary for secondary memory formation. Interestingly, we discovered in subsequent experiments that naïve CD8⁺ T cells display strikingly similar localization patterns to that of HP- memory cells. In the late phase immune response, true- memory CD8⁺ T cells are nearly absent from the splenic T cell zones, while a significant population of naïve or HP- memory subsets are retained in the PALS. As dendritic cells are crucial in providing activation, co-stimulatory, and memory differentiation signals to CD8⁺ T cell, we analyzed colocalization of T cells and DCs over the course of the immune response. In summary, HP-memory T cells provide protection without compromising the true-memory population, and the differential localization patterns among naïve, HP-, and true-memory cells in relation to DCs suggest that these cell types may influence their ability to compete and form a memory population.