Differential requirements for CD80/86–CD28 costimulation in primary and memory CD4 T cell responses to vaccinia virus

Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, United States.
Cellular Immunology (Impact Factor: 1.92). 10/2010; 266(2):130-4. DOI: 10.1016/j.cellimm.2010.09.008
Source: PubMed


Vaccinia virus infection can confer immunity to smallpox by inducing potent T cell and antibody responses. While the CD8 T cell response to vaccinia virus has been well characterized, less is known about factors required for priming and memory for the CD4 T cells. Focusing on two recently described epitopes, we show that after intranasal infection, both I1L and L4R epitopes are co-dominant during the acute response, but the I1L epitope dominates during memory. CD4 T cell priming was intact in the absence of CD80/86, however secondary responses were reduced. This contrasts with our previous data showing CD80/86-CD28 interaction is required for optimal primary and memory CD8 T cell responses. The absence of CD80/86 also changed the immunodominance hierarchy during memory, with the I1L and L4R responses becoming co-dominant in knockout mice. These data highlight different costimulatory requirements for primary CD4 and CD8 T cell responses to vaccinia virus.

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Available from: Leah M Rommereim, May 19, 2014
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    • "With respect to the profound impact on T cell function the downstream signaling cascades of the B7/CD28 pathway were further investigated in detail. While for the priming of CD4+ T cells the B7-1/B7-2-CD28 interaction is not always required [9], it is essential for primary and memory CD8+ T cell responses [4], [10], [11], [12]. CD28 not only provides T cell costimulation but also enhances the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT) activity, which is dependent on the p110 delta isoform of PI3K at the immunological synapse [13]. "
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