Alloreactive T cells are important mediators of rejection or tolerance of the transplanted organ. Detection and isolation of viable alloreactive T cells at the single cell level requires a cell surface marker specifically induced upon T cell receptor activation. In this study, a member of the TNFR-family, CD137 (4-1BB) was investigated for its potential to identify circulating alloreactive T cells in combination with phenotypic and functional analysis.
Optimal conditions for sensitive and specific detection of allogeneic-induced CD137 expression on circulating T cells were established. Thereafter, CD137+ alloreactive T cells were phenotypically and functionally characterized by multi-parameter flow-cytometry.
Alloantigen-induced CD137 expression identified both alloreactive CD8+ T cells (0.21±0.07%) and CD4+ T cells (0.21±0.05%). CD137+ alloreactive T cells were detected in different T cell subsets, including naÏve T cells, but were preferentially found in CD28+ T cells and not in the terminally differentiated T cell subsets. Upon allogeneic stimulation, the cytokine producing, but not proliferating capacity of T cells mainly resided within the CD137-expressing fraction. A minority of the CD137+ alloreactive cytokine producing T cells (<10%) produced any combination of IFN-Γ, IL-2 and TNF-Α. Poly-functional alloreactive T cells, defined by multiple cytokine expression, were infrequently observed. Numbers of alloreactive CD137+ cytokine+ T cells were positively associated with the number of HLA mismatches, although a substantial variation was observed.
Activation-induced CD137 expression allows for detection of the total cytokine producing, but not the total proliferating, alloreactive T cell compartment at the single cell level by multi-parameter flow-cytometry. CD137 expression might be a useful marker to gain more insight into the development of alloreactive T cells following kidney transplantation.
To cite this abstract in AMA style:Litjens N, Wit Ede, Baan C, Betjes M. CD137, a Marker To Detect the Total Alloreactive T Cell Compartment? [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/cd137-a-marker-to-detect-the-total-alloreactive-t-cell-compartment/. Accessed July 24, 2021.
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