CD8+ effector T cell migration to pancreatic islet grafts is dependent on cognate Ag presentation by donor graft cells1

• Published in: The Journal of immunology (1950) 2016-06, Vol.197 (4), p.1471-1476
• Main Authors: Zhang, Qianqian, Dai, Hehua, Yatim, Karim M., Abou-Daya, Khodor, Williams, Amanda L., Oberbarnscheidt, Martin H., Camirand, Geoffrey, Rudd, Christopher E., Lakkis, Fadi G.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1600832

Pancreatic islet transplantation is a promising therapy for diabetes, but acute rejection of the islets by host effector T cells has hindered clinical application. Here we addressed the mechanisms of CD8 + effector T cell migration to islet grafts since interrupting this step is key to preventing rejection. We found that effector T cell migration to re-vascularized islet transplants in mice is dependent on non-self Ag recognition rather than signaling via Gα i -coupled chemokine receptors. Presentation of non-self Ag by donor cells was necessary for migration, whereas Ag presentation by recipient cells was dispensable. We also observed that deficiency of SKAP1, an immune cell adaptor downstream of the TCR and important for integrin activation, prolongs allograft survival but does not reduce effector T cell migration to the graft. Therefore, effector T cell migration to transplanted islets is Ag-, not chemokine-, driven but SKAP1 does not play a critical role in this process.