Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: We have previously identified subsets of CD57+ T cells that are resistant to B7 costimulation blockade (CoB) in kidney transplant recipients. The objective of this study was to explore the phenotype and functional profile of allo-specific CD57+ cells during their memory and proliferative responses in vitro.
*Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy adults. PBMCs were stimulated with allogeneic mature dendritic cells for 16 hours and then stained for intracellular cytokines. The proliferative responses of T cells were evaluated by a VPD450-based assay. Analysis by polychromatic flow cytometry focused on the expression of the senescence marker CD57 and costimulatory markers CD28 and CD2 by allo-responsive T cells.
*Results: CD57+ cells were largely CCR7–CD45RA– effector memory cells (TEM, CD4+ 70.6±16.5%, CD8+ 61.4±19.3%). The proportion of allo-specific CD4+ memory T cells producing both TNF-a and IFN-g (0.26±0.18%) was significantly higher than that of unstimulated CD4+ cells (0.011±0.01%), and a large fraction of these dual cytokine producers was defined as CD28–CD57+ (41.5±16.1%) and CD28–CD57– (40.2±23.5%). Allo-specific CD4+ memory T cells producing TNF-a alone (1.47±1.57%) were significantly more enriched than those producing both TNF-a and IFN-g (p=0.016) and were predominantly CD28+CD57– (80.7±13.2%). Allo-specific memory CD8+TNF-a+IFN-g+ T cells (3.97±4.4%) were also primarily CD28–CD57+. A majority of proliferating CD4+ T cells was phenotypically characterized as CD28+CD57– (87.1±6.1%). A large fraction of proliferating CD8+ cells was defined as CD28+CD57–. Unlike their CD4+ counterparts, CD8+CD28–CD57+ cells demonstrated limited proliferative capacity (11.6±8.2%).
*Conclusions: In summary, allo-specific memory T cells distinguished by dual TNF-a/IFN-g cytokine production are largely CD57+ TEM cells but lack surface CD28 expression. A minority of proliferating allo-reactive cells, particularly CD8+ cells, are CD28–CD57+. Our data support the mechanism underlying CoB resistance observed clinically in transplant recipients.
To cite this abstract in AMA style:Lucander A, Xu H, Kirk A. Evaluating Allo-Specific CD57+ T Cells during Memory and Proliferative Responses [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/evaluating-allo-specific-cd57-t-cells-during-memory-and-proliferative-responses/. Accessed April 15, 2021.
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