The CD226/TIGIT axis is involved in T cell hypo-responsiveness appearance in long-term kidney transplant recipients

• Published in: Scientific reports 2022-07, Vol.12 (1), p.11821-11821, Article 11821
• Main Authors: Del Bello, Arnaud, Gouin, Anna, Chaubet, Camille, Kamar, Nassim, Treiner, Emmanuel
• Format: Article
• Language: English
• Subjects: 631/250; 692/4022; Antigens, Differentiation, T-Lymphocyte / immunology; CD4 antigen; CD4-Positive T-Lymphocytes; Cell proliferation; Cytokines / immunology; Effector cells; Human health and pathology; Humanities and Social Sciences; Humans; Immunosuppression; Interleukin 2; Kidney Transplantation; Kidney transplants; Life Sciences; Lymphocytes; Lymphocytes T; multidisciplinary; PD-1 protein; Receptors, Immunologic / immunology; Science; Science (multidisciplinary); T Lineage-Specific Activation Antigen 1; Transplantation Immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-15705-6

T cell exhaustion refers to a dysfunctional state in which effector T cells present a decreased ability to proliferate and to produce cytokines, while the co-expression of inhibitory receptors increases. We investigated global and donor-specific T cell responses in a cohort of stable, living-donor kidney transplant patients that received similar immunosuppression. After transplantation, an increase in the ratio of TIGIT + /CD226 + in mCD4 + T cells (r = 0.47, p = 0.01), and a decrease of CD226 + TIGIT-mCD4 + T cells was observed (r = − 0.55, p = 0.001). This leads to an increase of dysfunctional T cells in patients far from transplantation. In mCD8 + T cells, a decrease of IL-2 production after mitogenic stimulation was observed far from transplantation. Phenotypic analyses revealed an increase of mCD8 + T cells co-expressing PD-1 and TIGIT over time (r = 0.51, p = 0.02). After donor-specific stimulation, the ability of CD4 + T cells to proliferate was decreased compared with third parties. CD4 + T cells expressing CD226 and TIGIT were correlated with allospecific CD4 + proliferation (r = 0.68, p  = 0.04). Our study suggests that after kidney transplantation a T cell hyporesponsiveness appears over time, driven by a dysregulation of CD226/TIGIT axis in mCD4 + T cells, associated with an increase of PD1 + TIGIT + in mCD8 + T cells.