Fully functional memory CD8 T cells in the absence of CD4 T cells

Amanda L. Marzo, Vaiva Vezys, Kimberly D. Klonowski, Seung Joo Lee, Guruprasaadh Muralimohan, Meagan Moore, David F. Tough, Leo Lefrançois

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

The role of CD4 T cells in providing help to CD8 T cells in primary and secondary responses to infection remains controversial. Using recombinant strains of virus and bacteria expressing the same Ag, we determined the requirement for CD4 T cells in endogenous CD8 T cell responses to infection with vesicular stomatitis virus and Listeria monocytogenes (LM). Depletion of CD4 T cells had no effect on the frequency of primary or secondary vesicular stomatitis virus-specific CD8 T cells in either lymphoid or nonlymphoid tissues. In contrast, the primary LM-specific CD8 T cell response was CD4 T cell dependent. Surprisingly, the LM-specific CD8 T cell recall response was also CD4 T cell dependent, which correlated with a requirement for CD40/CD40L interactions. However, concomitant inhibition of CD40L and CD4 T cell removal revealed that these pathways may be operating independently. Importantly, despite the absence of CD4 T cells during the recall response or throughout the entire response, CD8 memory T cells were functional effectors and proliferated equivalently to their "helped" counterparts. These data call into question the contention that CD4 T cells condition memory CD8 T cells during the primary response and indicate that the principal role of CD4 T cells in generating CD8 memory cells after infection is augmentation of proliferation or survival through costimulatory signals.

Original languageEnglish (US)
Pages (from-to)969-975
Number of pages7
JournalJournal of Immunology
Volume173
Issue number2
DOIs
StatePublished - Jul 15 2004

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