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Increased Pretransplant Frequency of CD 28 + CD 4 + T EM Predicts Belatacept‐Resistant Rejection in Human Renal Transplant Recipients
Author(s) -
CortesCerisuelo M.,
Laurie S. J.,
Mathews D. V.,
Winterberg P. D.,
Larsen C. P.,
Adams A. B.,
Ford M. L.
Publication year - 2017
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14350
Subject(s) - belatacept , cd28 , medicine , effector , immunology , t cell , transplantation , kidney transplantation , kidney transplant , immune system
While most human T cells express the CD 28 costimulatory molecule constitutively, it is well known that age, inflammation, and viral infection can drive the generation of CD 28 null T cells. In vitro studies have demonstrated that CD 28 null cell effector function is not impacted by the presence of the CD 28 costimulation blocker belatacept. As such, a prevailing hypothesis suggests that CD 28 null cells may precipitate costimulation blockade‐resistant rejection. However, CD 28 + cells possess more proliferative and multifunctional capacity, factors that may increase their ability to successfully mediate rejection. Here, we performed a retrospective immunophenotypic analysis of adult renal transplant recipients who experienced acute rejection on belatacept treatment as compared to those who did not. Intriguingly, our findings suggest that patients possessing higher frequency of CD 28 + CD 4 + T EM prior to transplant were more likely to experience acute rejection following treatment with a belatacept‐based immunosuppressive regimen. Mechanistically, CD 28 + CD 4 + T EM contained significantly more IL ‐2 producers. In contrast, CD 28 null CD 4 + T EM isolated from stable belatacept‐treated patients exhibited higher expression of the 2B4 coinhibitory molecule as compared to those isolated from patients who rejected. These data raise the possibility that pretransplant frequencies of CD 28 + CD 4 + T EM could be used as a biomarker to predict risk of rejection following treatment with belatacept.