CD4+CD28null T cells are not alloreactive unless stimulated by interleukin‐15. Issue 2 (2nd October 2017)

• Record Type: Journal Article
• Authors: Dedeoglu, B.; Litjens, N. H. R.; Klepper, M.; Kraaijeveld, R.; Verschoor, W.; Baan, C. C.; Betjes, M. G. H.
• Is Part Of: American journal of transplantation. Volume 18:Issue 2(2018)
• Page Start: 341
• Page End: 350
• Publication Date: 2017-10-02
• Subjects: alloantigen -- basic (laboratory) research/science -- immunobiology -- immunosuppression/immune modulation -- kidney transplantation/nephrology -- T cell biology; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.14480
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Proinflammatory, cytotoxic CD4 + CD28 null T cells can be substantially expanded in patients with end‐stage renal disease. These cells have been associated with the risk for rejection, but their alloreactive potential is unknown. CD4 + CD28 null T cells were stimulated with HLA‐mismatched antigen presenting cells in the absence/presence of exogenous cytokines. Alloreactive potential was evaluated based on proliferation, degranulation, cytotoxicity, and cytokine production. Further, their suppressive capacity was assessed by measuring inhibition of proliferating alloreactive CD28 + T cells. CD4 + CD28 null T cells contained alloreactive (CD137 + ) T cells but did not proliferate in response to allogeneic stimulation, unless interleukin (IL)‐15 was added. However, they could proliferate on stimulation with cytomegalovirus antigen without exogenous cytokines. IL‐15 increased the frequency of proliferating alloreactive CD4 + CD28 null T cells to 30.5% without inducing CD28 expression ( P < .05). After allogeneic stimulation together with IL‐15 and IL‐21, frequency of degranulating CD107a + CD4 + CD28 null T cells increased significantly from 0.6% to 5.8% ( P < .001). Granzyme B and perforin positivity remained similar, but production of interferon‐γ and tumor necrosis factor‐α increased by the combination of IL‐15 and IL‐21 ( P < .001 and P < .05, respectively). Finally, CD4 + CD28 null T cells did not show significant suppression. Thus, CD4 + CD28 null T cells represent a population with absent alloreactivity unless IL‐15 is present. Abstract : CD4+CD28null T cells can become alloreactive when the proper conditions are met, especially in the presence of IL‐15, and IL‐21 can enhance the cytotoxic potential of CD4+CD28null T cells.