Diaz Luis A, Pai Rajiv, Endres Judith, Anthony Paul, Duzyj Christina, Bishu Shree, Morita Yoshitaka, Fox David A
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, 48109, USA.
J Lab Clin Med. 2003 Sep;142(3):149-57. doi: 10.1016/S0022-2143(03)00101-X.
The extent of interaction between human T-lymphocytes and xenogeneic antigen-presenting cells (APCs) is species-dependent. A successful interaction requires high-affinity receptor-ligand pairing across species and recognition of antigens presented by foreign major histocompatibility complex (MHC). A deficient human T-lymphocyte response to xenogeneic cells is likely the result of a defect in these interactions. However, the requirements for a T-cell response to superantigen (SAg) may differ from those of other T-cell responses. Using irradiated murine splenocytes, which are believed to be incapable of eliciting human T-cell responses, and porcine aortic endothelial cells (PAECs) as the APC populations, we studied the human T-lymphocyte response to antigens presented by these cells. Direct proliferation of human T-lymphocytes to SAg presented by murine APCs was demonstrated; it was blocked by anti-human LFA-1 and anti-murine MHC class II but not by anti-human MHC class II. PAECs also presented SAg to human T-cells, generating a proliferative response greater than the primary response to porcine xenoantigen. Culture of human T-cells with murine splenocytes or PAECs and SAg Staphylococcus enterotoxin A (SEA) for 7 days primed human T-cells to proliferate in a secondary culture in response to autologous APCs. This autologous secondary response was human MHC class II-dependent and was inhibited by anti-human LFA-1, anti-human CD2, and anti-human CD98. Surprisingly, both of these responses were also blocked by anti-SEA, suggesting that despite vigorous washing, a small amount of functionally important SAg was carried over from primary to secondary culture, probably bound to the surface of T-cells. Xenogeneic APCs, even those that fail to stimulate human T-cells directly, can serve as APCs for primary human T-cell responses. After such interactions T-cells can develop secondary responses in autologous interactions based on retention of minute amounts of SAg. Such interactions may have important implications for xenotransplantation.
人类T淋巴细胞与异种抗原呈递细胞（APC）之间的相互作用程度因物种而异。成功的相互作用需要跨物种的高亲和力受体-配体配对以及对外源主要组织相容性复合体（MHC）呈递的抗原的识别。人类T淋巴细胞对异种细胞反应不足可能是这些相互作用存在缺陷的结果。然而，T细胞对超抗原（SAg）反应的要求可能与其他T细胞反应不同。我们使用被认为无法引发人类T细胞反应的经辐照的小鼠脾细胞以及猪主动脉内皮细胞（PAEC）作为APC群体，研究了人类T淋巴细胞对这些细胞呈递抗原的反应。结果表明，人类T淋巴细胞可直接增殖以应对小鼠APC呈递的SAg；该增殖被抗人LFA-1和抗小鼠MHC II类抗体阻断，但未被抗人MHC II类抗体阻断。PAEC也能向人类T细胞呈递SAg，产生的增殖反应大于对猪异种抗原的初次反应。将人类T细胞与小鼠脾细胞或PAEC以及SAg葡萄球菌肠毒素A（SEA）培养7天，可使人类T细胞在二次培养中对自体APC产生增殖反应。这种自体二次反应依赖于人类MHC II类分子，并被抗人LFA-1、抗人CD2和抗人CD98抑制。令人惊讶的是，这两种反应也被抗SEA抗体阻断，这表明尽管经过充分洗涤，仍有少量功能重要的SAg从初次培养物带入二次培养物，可能与T细胞表面结合。异种APC，即使是那些不能直接刺激人类T细胞的APC，也可作为人类T细胞初次反应的APC。经过此类相互作用后，T细胞可基于微量SAg的保留在自体相互作用中产生二次反应。此类相互作用可能对异种移植具有重要意义。
