A subset of γδ T‐cell receptor‐positive cells produce T‐helper type‐2 cytokines and regulate mouse skin graft rejection following portal venous pretransplant preimmunization

Abstract

C3H/HeJ mice received B10.BR skin grafts following portal or lateral tail vein infusion of irradiated B10.BR spleen cells. Thereafter mice were injected with anti‐αβ or anti‐γδ T‐cell receptor (TCR) monoclonal antibody (mAb). Anti‐γδ TCR mAb abolished the increased graft survival afforded by portal venous (p.v.) immunization, and reversed the bias towards expression of mRNA for type‐2 cytokines [interleukin‐4 (IL‐4), IL‐10] seen in lymphoid tissue of p.v.‐immunized mice. When γδ TCR+ and αβ TCR+ cells were isolated from the intestinal epithelial compartment (IEL), liver or Peyer's Patch (PP) of p.v.‐immunized mice, the γδ TCR+ cells were found to be enriched in cells producing type‐2 cytokines on rechallenge with irradiated B10.BR cells in vitro. γδ TCR+ cells from p.v.‐immunized mice were further expanded in vitro with anti‐CD3 and cytokines (combined IL‐2 and IL‐4). Following expansion these cells were capable of adoptively transferring increased B10.BR skin graft survival to naive mice, and continued to show a bias in type‐2 cytokine synthesis after allostimulation in vitro. When γδ TCR chain expression was assessed in cells taken from p.v.‐immunized mice, or in cells expanded in culture, our data suggest that p.v. immunization leads to oligoclonal, not polyclonal, expansion of those γδ TCR+ cells involved in inhibition of graft rejection.

Selective, efficient modulation of activated CD4+ αβT cells by the novel humanized antibody GZ-αβTCR targeting human αβTCR

“…[57][58][59] In addition, γδT cells are crucial modulators of immune responses and decisive in the induction and maintenance of tolerance in various physiological settings [60][61][62][63] and can directly promote allograft survival. 64 GZ-αβTCR was well tolerated, congruent with the bland cytokine signature obtained in vitro when crosslinking αβT cell TCR with GZ-αβTCR. Both findings stand in clear contrast to the life-threatening cytokine release storms observed after OKT3 treatment.…”

Flow cytometric analysis of tumour‐infiltrating lymphocytes in patients with renal cell carcinoma

“…In tumour samples, NK cells accounted for 2.6-40.2% of lymphocytic infillymphocytes appeared to be negatively correlated with the intensity of the mononuclear infiltration, possibly trate. Within the same patient, either a high or low frequency of CD56+ CD16+ cells in the TIL population because the cd T cells have a regulatory function [18]. Recent evidence indicates that NK cells are not only did not reflect the values observed in peripheral blood.…”

Characterization of γδ T cell subsets in organ transplantation

“…Thus considerably insight has been gained on their tissue location, recognition pattern and effector functions. In experimental animal transplantation cd T cells appear to possess an immunoregulatory function [17,18]. Similarly, in a clinical context, cd T cells could also contribute to allogenic engraftment in both bone marrow transplantation [19] and kidney transplantation [20].…”