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* Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030; and
The Edward Jenner Institute for Vaccine Research, Compton, United Kingdom
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.
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M. A. Kutzler, T. M. Robinson, M. A. Chattergoon, D. K. Choo, A. Y. Choo, P. Y. Choe, M. P. Ramanathan, R. Parkinson, S. Kudchodkar, Y. Tamura, et al. Coimmunization with an Optimized IL-15 Plasmid Results in Enhanced Function and Longevity of CD8 T Cells That Are Partially Independent of CD4 T Cell Help J. Immunol., July 1, 2005; 175(1): 112 - 123. [Abstract] [Full Text] [PDF]
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T. N. J. Bullock and H. Yagita Induction of CD70 on Dendritic Cells through CD40 or TLR Stimulation Contributes to the Development of CD8+ T Cell Responses in the Absence of CD4+ T Cells J. Immunol., January 15, 2005; 174(2): 710 - 717. [Abstract] [Full Text] [PDF]
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