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(The FASEB Journal. 2008;22:lb532)
© 2008 FASEB
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lb532

Protective Immunity in Transplant Recipients

Prasad Mulupuri1, Tania Gourley1, Adam Popkowski1, Aneesh Mehta2, Beth Begley2, Cynthia Breeden2, Christian Larsen2 and Rafi Ahmed1

1 Microbiology and Immunology,
2 Emory Transplant Center and Department of Surgery, EMORY University, Atlanta, GA

ABSTRACT

To better understand the effect of chronic immunosuppressive therapies on protective immunity in transplant recipients, analysis of T cell subsets including antigen-specific memory cells was performed at the time and various times after transplantation (3, 6, 9 and 12 months). A group of transplant recipients showed a maintenance or elevation in CMV-specific T cells, despite being on a Tacrolimus immuno-suppression. This elevation in CMV-specific T cells is possibly due to exposure or due to reactivation of virus. CMV-specific CD8 T cells from a transplant recipient showed functional exhaustion (as measured by lack of TNFa and IL-2 production).

We also studied patients undergoing T-cell depletion with anti-thymocyte globulin (ATG), to understand the dynamics and characteristics of repopulating T cells. Overall, T cells were homogeneously depleted by ATG. However, repopulation of CD8 T cells were variable (3–12 months) and were of an effector memory phenotype (CD45RA- CCR7-). CMV and EBV specific T-cells were reduced at 3 months after ATG induction. At later time points there was an elevation in CMV-specific T cells, possibly due to loss of protective immunity and virus reactivation. These results suggest that patients on active immuno-suppression can mount antigen-specific immune responses and future experiments will be aimed at determining phenotype and functional quality of these cells.





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