Hirota T, Hirose H, Iwata H, Kanetake K, Murakawa S, Sasaki E, Takagi H, Bando M, Hamaoka T, Fujiwara H
First Department of Surgery, Gifu University Medical School, Japan.
Transplantation. 1997 Mar 15;63(5):705-10. doi: 10.1097/00007890-199703150-00016.
Alloantigens are recognized by T cells either through a direct pathway, which involves recognition of alloantigens expressed on allogeneic antigen-presenting cells (APC), or through an indirect pathway, which involves recognition of processed alloantigens presented by self APC. We investigated whether rat xenoantigens are also recognized by direct (xenogeneic APC-restricted) and/or indirect (self APC-restricted) pathways. C57BL/6 (B6) mouse anti-F344 or WKAH rat mixed lymphocyte reactions (MLRs) were partially inhibited by addition of either anti-mouse CD4 or CD8 monoclonal antibody (mAb) and almost completely blocked in the presence of both mAbs. These xenogeneic MLRs were almost completely inhibited by simultaneous depletion of both self and xeno APCs and only partially suppressed by the elimination of either type of APC, indicating that freshly prepared splenic mouse T cells can recognize rat xenoantigens through both direct and indirect pathways. Anti-F334 T cell lines were generated from B6 anti-F344 MLR cultures, and four CD4+ and four CD8+ T cell clones were isolated from these parental lines. The parental lines and those derived T cell clones were tested for their ability to proliferate depending on the presence of F344 APC. Proliferation of CD8 clones by stimulation with F344 APC was inhibited by the addition of anti-rat class I MHC mAb but not of anti-class II MHC mAbs. Conversely, proliferation of CD4 clones was reduced by addition of anti-class II MHC mAbs. Thus, these results indicate that xeno (rat)-reactive mouse T cells recognize xenoantigens via both indirect (self APC-restricted) and direct (xeno APC-restricted) pathways and that both CD4 and CD8 subsets of T cells participate in a direct pathway of xenoantigen recognition.
同种异体抗原可通过直接途径被T细胞识别，该途径涉及识别表达于异基因抗原呈递细胞（APC）上的同种异体抗原；也可通过间接途径被识别，此途径涉及识别由自身APC呈递的经处理的同种异体抗原。我们研究了大鼠异种抗原是否也通过直接（异种APC限制）和/或间接（自身APC限制）途径被识别。通过添加抗小鼠CD4或CD8单克隆抗体（mAb），C57BL/6（B6）小鼠抗F344或WKAH大鼠混合淋巴细胞反应（MLR）受到部分抑制，而在两种mAb同时存在时几乎完全被阻断。这些异种MLR在自身和异种APC同时缺失时几乎完全被抑制，仅去除任何一种APC时仅部分受到抑制，这表明新制备的脾小鼠T细胞可通过直接和间接途径识别大鼠异种抗原。从B6抗F344 MLR培养物中产生抗F334 T细胞系，并从这些亲代系中分离出四个CD4 +和四个CD8 + T细胞克隆。根据F344 APC的存在情况，检测亲代系及其衍生的T细胞克隆的增殖能力。添加抗大鼠I类MHC mAb可抑制F344 APC刺激引起的CD8克隆增殖，但添加抗II类MHC mAb则无此作用。相反，添加抗II类MHC mAb可降低CD4克隆的增殖。因此，这些结果表明，异种（大鼠）反应性小鼠T细胞通过间接（自身APC限制）和直接（异种APC限制）途径识别异种抗原，并且T细胞的CD4和CD8亚群均参与异种抗原识别的直接途径。
