虽然早期移植人类胰岛细胞植入以及存活已经获得成功，但是移植胰岛细胞远期的丢失已经显现成为重要的临床问题。CD8+T细胞能够在无CD4+T细胞的帮助下破坏移植物且对于常规的免疫抑制疗法失效。先前的研究提示胰岛细胞移植物并不会通过（非CD4依赖性）CD8依赖性途径原发性产生排斥反应。该研究的目的在于明确是否同种异体反应性非CD4依赖的CD8+T细胞通过外生性刺激能够能够导致长期移植物的丢失。受者采用肝内胰岛细胞种植（胰岛“受体”），联合短期的免疫抑制治疗包括供者特异性的输注（DST）以及抗CD154单抗。在获得稳定的长期胰岛移植物功能60-90天后，受者开始接受供者匹配的肝细胞移植物，其能够活化（非CD4依赖）CD8+T细胞。同基因的移植胰岛细胞在局部存在供者匹配的肝细胞情况下非常脆弱。移植胰岛细胞丢失是由于同种特异性的免疫破坏，其为CD8依赖性，而非CD4依赖性。在移植时选择特异性的免疫治疗同时移植CD4和CD8依赖的免疫通路能够同时保护移植物近期和远期免受免疫系统的破坏。

Despite success of early islet allograft engraftment and survival in humans, late islet allograft loss has emerged as an important clinical problem. CD8+ T cells that are independent of CD4+ T cell help can damage allograft tissues and are resistant to conventional immunosuppressive therapies. Previous work demonstrates that islet allografts do not primarily initiate rejection by the (CD4-independent) CD8-dependent pathway. This study was performed to determine if activation of alloreactive CD4-independent, CD8+ T cells, by exogenous stimuli, can precipitate late loss of islet allografts. Recipients were induced to accept intrahepatic islet allografts (islet 'acceptors') by short-term immunotherapy with donor-specific transfusion (DST) and anti-CD154 mAb. Following the establishment of stable long-term islet allograft function for 60-90 days, recipients were challenged with donor-matched hepatocellular allografts, which are known to activate (CD4-independent) CD8+ T cells. Allogeneic islets engrafted long-term were vulnerable to damage when challenged locally with donor-matched hepatocytes. Islet allograft loss was due to allospecific immune damage, which was CD8- but not CD4-dependent. Selection of specific immunotherapy to suppress both CD4- and CD8-dependent immune pathways at the time of transplant protects islet allografts from both early and late immune damage.