Rapamycin ameliorates the CTLA4-Ig-mediated defect in CD8(+) T cell immunity during gammaherpesvirus infection.

ABSTRACT: Latent viral infections are a major concern among immunosuppressed transplant patients. During clinical trials with belatacept, a CTLA4-Ig fusion protein, patients showed an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder, thought to be due to a deficient primary CD8(+) T cell response to the virus. Using a murine model of latent viral infection, we observed that rapamycin treatment alone led to a significant increase in virus-specific CD8(+) T cells, as well as increased functionality of these cells, including the ability to make multiple cytokines, while CTLA4-Ig treatment alone significantly dampened the response and inhibited the generation of polyfunctional antigen-specific CD8(+) T cells. However, the addition of rapamycin to the CTLA4-Ig r

SUBMITTER: Pinelli DF 

PROVIDER: S-EPMC5389899 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature