Helper T cells are critical for protective immunity, CD8 T cell memory, and CD4 recall responses required for effective vaccines. Despite the importance of CD4 T cells in immune responses, studies examining T cell responses to Listeria monocytogenes have focused primarily on CD8 T cells. We have developed two CD4 T cell transgenic mouse lines specific for an immunodominant L. monocytogenes epitope, providing a novel means of examining CD4 T cell activation and memory formation. These mice, called LLO118 and LLO56, differ by only 14 amino acids in their TCR sequences and have identical responses to peptide and L. monocytogenes infection in vitro. Comparison of the in vivo CD4 T cell responses to L. monocytogenes infection revealed LLO118 T cells proliferate much more strongly in a primary infection and cause a more robust CD8 response to secondary infection than LLO56. Surprisingly, we found that LLO56 has a superior CD4 recall response to secondary infection. CD5 expression and TCR downregulation correlate with the discordant primary and secondary responses. CD5 is higher in LLO56 prior to infection whereas LLO118 TCR levels downregulate more after the primary infection. Thus, a strong initial proliferation results in a better CD8 recall response, but a decreased CD4 recall response due to downregulated TCR levels. These findings imply that there are two populations of helper T cells: one that works best in primary responses and another in the secondary response.
- Copyright © 2011 by The American Association of Immunologists, Inc.