Transplantation is the only curative treatment for patients with kidney failure but it poses unique immunological challenges that must be overcome to prevent allograft rejection and ensure long-term graft survival. Alloreactive T cells are important contributors to graft rejection, and a clearer understanding of the mechanisms by which these cells recognize donor antigens — through direct, indirect or semi-direct pathways — will facilitate their therapeutic targeting. Post-T cell priming rejection responses can also be modified by targeting pathways that regulate T cell trafficking, survival cytokines or innate immune activation. Moreover, the quantity and quality of donor-reactive memory T cells crucially shape alloimmune responses. Of note, many fundamental concepts in transplant immunology have been derived from models of infection. However, the programmed differentiation of allograft-specific T cell responses is probably distinct from that of pathogen-elicited responses, owing to the dearth of pathogen-derived innate immune activation in the transplantation setting. Understanding the fundamental (and potentially unique) immunological pathways that lead to allograft rejection is therefore a prerequisite for the rational development of therapeutics that promote transplantation tolerance.

移植是肾衰竭患者的唯一治疗方法，但它带来了独特的免疫学挑战，必须克服这些挑战才能防止同种异体移植物排斥并确保移植物长期存活。同种反应性 T 细胞是移植物排斥的重要贡献者，更清楚地了解这些细胞通过直接、间接或半直接途径识别供体抗原的机制将有助于其治疗靶向。T 细胞启动后的排斥反应也可以通过靶向调节 T 细胞运输、存活细胞因子或先天免疫激活的途径来改变。此外，供体反应性记忆 T 细胞的数量和质量对同种免疫反应至关重要。值得注意的是，移植免疫学中的许多基本概念都源自感染模型。然而，由于移植环境中缺乏病原体衍生的先天免疫激活，同种异体移植物特异性 T 细胞反应的程序化分化可能与病原体引起的反应不同。因此，了解导致同种异体移植排斥的基本（且可能是独特的）免疫学途径是合理开发促进移植耐受的疗法的先决条件。