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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.

Original publication




Journal article


J Immunol

Publication Date





5188 - 5197


Adoptive Transfer, Animals, CD8-Positive T-Lymphocytes, Cell Communication, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Interleukin-12, Interleukin-2, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Poxviridae Infections, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Helper-Inducer, Vaccinia virus