Fully Functional Memory CD8 T Cells in the Absence of CD4 T Cells

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 v...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-07, Vol.173 (2), p.969-975
Main Authors: Marzo, Amanda L, Vezys, Vaiva, Klonowski, Kimberly D, Lee, Seung-Joo, Muralimohan, Guruprasaadh, Moore, Meagan, Tough, David F, Lefrancois, Leo
Format: Article
Language:English
Subjects:
Animals
CD4-Positive T-Lymphocytes - immunology
CD40 Ligand - metabolism
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Immunologic Memory - immunology
Immunologic Memory - physiology
Listeria monocytogenes
Listeriosis - immunology
Mice
Vesicular stomatitis virus
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.173.2.969