CD4 T cells are required for CD8 T cell survival during both primary and memory recall responses.
The role of CD4 T cell help in primary and secondary CD8 T cell responses to infectious pathogens remains incompletely defined. The primary CD8 T response to infections was initially thought to be largely independent of CD4 T cells, but it is not clear why some primary, pathogen-specific CD8 T cell responses are CD4 T cell dependent. Furthermore, although the generation of functional memory CD8 T cells is CD4 T cell help dependent, it remains controversial when the "help" is needed. In this study, we demonstrated that CD4 T cell help was not needed for the activation and effector differentiation of CD8 T cells during the primary response to vaccinia virus infection. However, the activated CD8 T cells showed poor survival without CD4 T cell help, leading to a reduction in clonal expansion and a diminished, but stable CD8 memory pool. In addition, we observed that CD4 T cell help provided during both the primary and secondary responses was required for the survival of memory CD8 T cells during recall expansion. Our study indicates that CD4 T cells play a crucial role in multiple stages of CD8 T cell response to vaccinia virus infection and may help to design effective vaccine strategies.
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Patricia
P
Novy
Michael
M
Quigley
Xiaopei
X
Huang
Yiping
Y
Yang
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002470:Cell Survival; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D014615:Vaccinia / Q000276:immunology*
D015704:CD4 Antigens