Cutting edge: persistent viral infection prevents tolerance induction and escapes immune control following CD28/CD40 blockade-based regimen
- PMID: 12421910
- DOI: 10.4049/jimmunol.169.10.5387
Cutting edge: persistent viral infection prevents tolerance induction and escapes immune control following CD28/CD40 blockade-based regimen
Abstract
A continuing concern with CD28 and/or CD40 blockade-based strategies to induce tolerance and mixed chimerism is their potential to disrupt protective immunity to preexisting infections. In this report, we find that preexisting persistent infection with lymphocytic choriomeningitis virus (LCMV) clone 13 prevents the induction of tolerance, mixed chimerism, and donor-reactive T cell deletion. Mice continue to be refractory to tolerance induction even after viremia has been resolved and virus is present only at very low levels in peripheral tissues. Conversely, we find that the full tolerance regimen, or costimulation blockade alone, specifically inhibits already ongoing antiviral immune responses, leading to an inability to control viremia. These findings suggest that ongoing T cell responses continue to depend on costimulatory interactions in the setting of a chronic infection and provide insight into potential risks following costimulation blockade posed by chronic or latent viral infections such as hepatitis C, EBV, and CMV.
Similar articles
-
Viral abrogation of stem cell transplantation tolerance causes graft rejection and host death by different mechanisms.J Immunol. 2002 Jun 15;168(12):6047-56. doi: 10.4049/jimmunol.168.12.6047. J Immunol. 2002. PMID: 12055213
-
CD4 T cell-mediated alloresistance to fully MHC-mismatched allogeneic bone marrow engraftment is dependent on CD40-CD40 ligand interactions, and lasting T cell tolerance is induced by bone marrow transplantation with initial blockade of this pathway.J Immunol. 2001 Mar 1;166(5):2970-81. doi: 10.4049/jimmunol.166.5.2970. J Immunol. 2001. PMID: 11207246
-
Costimulation blockade, busulfan, and bone marrow promote titratable macrochimerism, induce transplantation tolerance, and correct genetic hemoglobinopathies with minimal myelosuppression.J Immunol. 2001 Jul 15;167(2):1103-11. doi: 10.4049/jimmunol.167.2.1103. J Immunol. 2001. PMID: 11441122
-
[Studies on the induction of transplantation tolerance and immune reconstitution through combined strategies].Beijing Da Xue Xue Bao Yi Xue Ban. 2007 Oct 18;39(5):547-9. Beijing Da Xue Xue Bao Yi Xue Ban. 2007. PMID: 17940578 Review. Chinese.
-
T cell responses to viral infections: lessons from lymphocytic choriomeningitis virus.Immunol Res. 2002;26(1-3):309-21. doi: 10.1385/IR:26:1-3:309. Immunol Res. 2002. PMID: 12403369 Review.
Cited by
-
Reprogramming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection.J Clin Invest. 2006 Jun;116(6):1675-85. doi: 10.1172/JCI26856. Epub 2006 May 18. J Clin Invest. 2006. PMID: 16710479 Free PMC article.
-
Innate pathways of immune activation in transplantation.J Transplant. 2010;2010:826240. doi: 10.1155/2010/826240. Epub 2010 Aug 31. J Transplant. 2010. PMID: 20871653 Free PMC article.
-
Immunosuppressive mechanisms during viral infectious diseases.Methods Mol Biol. 2011;677:431-47. doi: 10.1007/978-1-60761-869-0_27. Methods Mol Biol. 2011. PMID: 20941625 Free PMC article.
-
Resilience of T cell-intrinsic dysfunction in transplantation tolerance.Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23682-23690. doi: 10.1073/pnas.1910298116. Epub 2019 Nov 4. Proc Natl Acad Sci U S A. 2019. PMID: 31685610 Free PMC article.
-
Induction of tolerance for islet transplantation for type 1 diabetes.Curr Diab Rep. 2003 Aug;3(4):329-35. doi: 10.1007/s11892-003-0026-9. Curr Diab Rep. 2003. PMID: 12866997 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
