biostudies-literatureWeber KSNIAID NIH HHS9511-6https://www.ebi.ac.uk/biostudies/studies/S-EPMC3386110biostudies-literatureUnknown109(24)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.Proceedings of the National Academy of Sciences of the United States of AmericaDistinct CD4+ helper T cells involved in primary and secondary responses to infection.PMC3386110P01 AI071195U54 AI057160R01 AI091878T32 AI007290R01 AI024157Li QJCampbell JDPersaud SPDavis MMAllen PMWeber KSfalseDistinct CD4+ helper T cells involved in primary and secondary responses to 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.2012-01-01T00:00:00Z2012 Jun2021-02-20T11:16:13Z2019-03-27T00:55:03ZS-EPMC33861102264534910.1073/pnas.1202408109