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 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.
Marzo
Amanda L
AL
Division of Immunology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Vezys
Vaiva
V
Klonowski
Kimberly D
KD
Lee
Seung-Joo
SJ
Muralimohan
Guruprasaadh
G
Moore
Meagan
M
Tough
David F
DF
Lefrançois
Leo
L
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology* / Q000502:physiology; D008088:Listeriosis / Q000276:immunology; D051379:Mice
D023201:CD40 Ligand