*Purpose: CD28-CD8+ T cells represent a differentiated CD8+ T cell subset that is found to be increased in various conditions associated with chronic antigenic stimulation such as aging, chronic viral infections, autoimmune diseases, cancers, and allotransplantation. In this study, we look for an association between CD28-CD8+ T cell levels and kidney allograft rejection.

*Methods: Using multivariate models, we analyzed a large cohort of 1032 kidney transplant patients in whom 1495 kidney graft biopsies were performed concomitant with a peripheral blood leukocyte phenotyping by flow cytometry. We investigated the association between the level of CD28-CD8+ T cells in the blood and the diagnosis of graft rejection according to the recent Banff classification of renal allograft pathology.

*Results: We found that antibody-mediated rejection (ABMR) of kidney allograft was associated with a significant increase in the percentage as well as the absolute number of CD28-CD8+ T cells in the peripheral blood at the time of biopsy. The confounder-adjusted mean difference of log percentage and log absolute value of CD28-CD8+ T cells between the ABMR group and the normal group were 0.29 (p=0.0004) and 0.38 (p=0.0004), respectively. Otherwise stated, the percentage and absolute number CD28-CD8+ T cells were 34% and 46% higher in AMBR patients compared to patients with normal histology, respectively. Further lymphocyte phenotyping revealed that the majority of those cells are effector memory re-expressing CD45RA (TEMRA) T-cells. Compared to CD28+CD8+ T cells, CD28-CD8+ T cells respond more vigorously to TCR stimulation. A subset of CD28-CD8+ T cells also express Fc gamma receptor IIIa (CD16) and degranulate upon CD16 ligation.

*Conclusions: Collectively, our findings suggest that differentiated CD28-CD8+ T cells participate in ABMR and further studies are warranted to clarify the immunological role of this T cell subset in kidney graft rejection.

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