Th cells act via two synergistic pathways to promote antiviral CD8+ T cell responses.
The mechanisms of how Th cells promote CD8(+) T cell responses during viral infections are largely unknown. In this study, we unraveled the mechanisms of T cell help for CD8(+) T cell responses during vaccinia virus infection. Our results demonstrate that Th cells promote vaccinia virus-specific CD8(+) T cell responses via two interconnected synergistic pathways: First, CD40L expressed by activated CD4(+) T cells instructs dendritic cells to produce bioactive IL-12p70, which is directly sensed by Ag-specific CD8(+) T cells, resulting in increased IL-2Rα expression. Second, Th cells provide CD8(+) T cells with IL-2, thereby enhancing their survival. Thus, Th cells are at the center of an important communication loop with a central role for IL-2/IL-2R and bioactive IL-12.
Wiesel
Melanie
M
Institute for Microbiology, Swiss Federal Institute of Technology Zürich (ETH Zürich), Zürich, Switzerland.
Joller
Nicole
N
Ehlert
Anna-Katharina
AK
Crouse
Josh
J
Spörri
Roman
R
Bachmann
Martin F
MF
Oxenius
Annette
A
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D018664:Interleukin-12 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011213:Poxviridae Infections / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology
D007376:Interleukin-2; D018664:Interleukin-12