Abstract
Abstract Polyfunctional CD8 T cells produce multiple cytokines and effector molecules in order to control chronic viral infections, such as cytomegalovirus (CMV), a cause of allograft damage in transplant patients. Healthy individuals resolve primary CMV infection rapidly and control viral reactivation with memory T cells. IFNγ production by CD8 T cells protects from CMV, but the role of polyfunctional T cells in immunosuppressed transplant patients is not fully understood. We measured responses to CMV polypeptides IE-1 and pp65 to characterize the effects of T cell depletion on T cell specificity and polyfunctionality. In this study we identified polyfunctionality as co-expression of IFNγ, TNFα, and/or the degranulation marker CD107a. We analyzed T cell responses in pre- to a year post-transplant PBMC samples from cardiac and renal transplant patients. Treatment included anti-viral prophylaxis and 3 drug immunosuppression, with T cell depleting induction therapy in some patients. The 3 normal donors and 12 pre-transplant samples analyzed fall into 3 groups on the basis of IE-1 and pp65 specificity: equal response to both or dominant for either IE-1 or pp65. Almost all cells with exactly two functions were TNFα+. In some patients, lymphodepletion led to an early loss of polyfunctional T cells. However, polyfunctional CD8 T cells returned to pre-transplant levels by day 180. In addition, 3 patients displayed shifts from their pre-transplant IE-1 vs pp65 specificity post-transplant, while specificity was consistent over a year post-transplant in the other 8. In conclusion, pre-transplant TNFα expression is predictive of polyfunctionality, and further study is needed to determine the effect of T cell depletion on fine antigen specificity.
Published Version
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