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Distinct CD4⁺ helper T cells involved in primary and secondary responses to infection

Weber, K. Scott, Li, Qi-Jing, Persaud, Stephen P., Campbell, Jeff D., Davis, Mark M., Allen, Paul M.
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.24 pp. 9511-9516
CD4-positive T-lymphocytes, Listeria monocytogenes, epitopes, immunity, secondary infection
Helper T cells are critical for protective immunity, CD8 ⁺ T-cell memory, and CD4 ⁺ recall responses, but whether the same or distinct CD4 ⁺ T cells are involved in these responses has not been established. Here we describe two CD4 ⁺ T cells, LLO118 and LLO56, specific for an immunodominant Listeria monocytogenes epitope, with dramatically different responses to primary and secondary infection. Comparing in vivo responses, LLO118 T cells proliferate more strongly to primary infection, whereas surprisingly, LLO56 has a superior CD4 ⁺ recall response to secondary infection. LLO118 T cells provide more robust help for CD8 ⁺ T-cell responses to secondary infection than LLO56. We found no detectable differences in antigen sensitivity, but naive LLO118 T cells have much lower levels of CD5 and their T-cell receptor levels are dramatically down-regulated after their strong primary response. Thus, distinct CD4 ⁺ helper T cells are specialized to help either in primary or secondary responses to infection.