Chronic infection affects development of protective memory CD4 T cells in murine malaria

Both malaria infections and vaccines are reported to induce only short‐lived immunity; possibly due to lack of T cell memory, as both T cell cytokines and B cell help are critical. Using a T cell receptor transgenic mouse, where CD4 T cells recognize Plasmodium chabaudi, Merozoite Surface Protein‐1 (1157‐1171/I‐E d ); we investigated development of CD4 T cell memory and its part in protection against infection and pathology in chronic and drug‐treated infection. We observed that specific memory cells, as defined by surface phenotype (CD44 hi , CD25 − , IL7‐Rα hi , CD62L hi/lo ) and cytokine production (IFNγ hi , IL‐2 hi ) accumulated after one infection, and that although they were rapidly activated in a second infection, they did not proliferate faster than in a first infection. In a RAG transfer model, we observed that memory T cells from a drug‐limited infection allowed clearance of a challenge infection faster than naïve cells, but can increase pathology. Interestingly, chronic infection changed both memory phenotype and protective capacity of specific CD4 cells and maintained a memory population with a phenotype similar to effector cells (CD44 hi , IL7Rα − ) that protected no better than naïve CD4 T cells. (MRC)