Journal
JOURNAL OF IMMUNOLOGY
Volume 180, Issue 5, Pages 3190-3200Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.180.5.3190
Keywords
-
Categories
Funding
- NIAID NIH HHS [P01 AI04464409] Funding Source: Medline
Ask authors/readers for more resources
Therapies that control largely T cell-dependent allograft rejection in humans also possess the undesirable effect of impairing T cell function, leaving transplant recipients susceptible to opportunistic viruses. Prime among these opportunists are the ubiquitous herpesviruses. To date, studies are lacking that address the effect of viruses that establish a true latent state on allograft tolerance or the effect of tolerance protocols on the immune control of latent viruses. By using a mixed chimerism-based tolerance-induction protocol, we found that mice undergoing latent infection with gamma HV68, a murine gamma-herpesvirus closely related to human gamma-herpesviruses such as EBV and Kaposi's sarcoma-associated herpesvirus, significantly resist tolerance to allografts. Limiting the degree of virus reactivation or innate immune response did not reconstitute chimerism in latently infected mice. However, gamma HV68-infected mice showed increased frequency of CD8(+) T cell alloreactivity and, interestingly, expansion of virus-induced, alloreactive, effector/effector memory TCR V beta 4(+)CD8(+) T cells driven by the gamma HV68-M1 gene was associated with resistance to tolerance induction in studies using gamma HV68-M1 mutant virus. These results define the viral gene and immune cell types involved in latent infection-mediated resistance to allograft tolerance and underscore the influence of latent herpesviruses on allograft survival.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available