Lowry R P, Gurley K E
Transplantation. 1983 Oct;36(4):405-11.
The role of T and B lymphocytes in rejection of cardiac allografts bearing isolated major histocompatibility complex (MHC) subregion RT1.B/D encoded class II "Ia" disparities was investigated using natural and congenic recombinant inbred rats (RP, PVG RT1r1). RT1.B/D-disparate heart grafts were shown in 3 strain combinations (RP leads to WF, WF leads to [RP x PVG RT1l] F1, and PVG RT1r1 leads to PVG RT1 alpha) to induce a brisk humoral response (complement-dependent cytotoxicity [CDC] titers greater than 2(6] with specificity for class II determinants as evidenced by strain and tissue distribution of susceptible targets. Cytotoxic T cells (Tc) generated in parallel effected equivalent lysis (in the 4-hr 51Cr-release LMC assay) of con A and lipopolysaccharide (LPS) blasts of the same strains. Specificity of Tc for class II determinants was demonstrable by specific inhibition of killing (congruent to 50%) by anti-Ia antibody preparations (monoclonal 0X4 and antiserum ATH anti-ATL) with specificity for class II products of MHC subregions RT1.B and RT1.D, respectively. Adoptive transfer studies revealed that antibody and cytotoxic effectors (W3/25+, OX8+) with specificity for class II "Ia" determinants, though potentially injurious, are not required for rejection of cardiac allografts transplanted across isolated RT1.B/D disparities (RP leads to WF) because transfer even of small numbers (0.5 X 10(6] of helper T cells (W3/25+, OX8-) previously shown to be responsible for adoptive transfer of delayed type hypersensitivity to alloantigen, effected rejection in the absence of detectable antibody or Tc. In the immune response to alloantigen both cytotoxic T cell generation and a humoral immune response develop in parallel with that other form of cellular immunity, akin to classic delayed or tuberculinlike hypersensitivity, itself potentially a potent effector mechanism in organ allograft rejection.
利用天然的和同源重组近交系大鼠（RP、PVG RT1r1），研究了T淋巴细胞和B淋巴细胞在排斥携带分离的主要组织相容性复合体（MHC）亚区RT1.B/D编码的Ⅱ类“Ia”差异的心脏同种异体移植物中的作用。在3种品系组合（RP→WF、WF→[RP×PVG RT1l]F1和PVG RT1r1→PVG RT1α）中，RT1.B/D不相容的心脏移植物显示可诱导强烈的体液反应（补体依赖细胞毒性[CDC]滴度大于2⁶，对Ⅱ类决定簇具有特异性，这由敏感靶标的品系和组织分布证明）。同时产生的细胞毒性T细胞（Tc）对相同品系的刀豆蛋白A和脂多糖（LPS）刺激的细胞具有同等程度的裂解作用（在4小时⁵¹Cr释放淋巴细胞介导的细胞毒试验中）。通过分别对MHC亚区RT1.B和RT1.D的Ⅱ类产物具有特异性的抗Ia抗体制剂（单克隆抗体0X4和抗血清ATH抗ATL）特异性抑制杀伤作用（约50%），可证明Tc对Ⅱ类决定簇的特异性。过继转移研究表明，对Ⅱ类“Ia”决定簇具有特异性的抗体和细胞毒性效应细胞（W3/25⁺、OX8⁺）虽然可能具有损伤性，但对于跨越分离的RT1.B/D差异（RP→WF）移植的心脏同种异体移植物的排斥并非必需，因为即使转移少量（0.5×10⁶）先前已证明负责对同种异体抗原进行迟发型超敏反应过继转移的辅助性T细胞（W3/25⁺、OX8⁻），在没有可检测到的抗体或Tc的情况下也能实现排斥。在对同种异体抗原的免疫反应中，细胞毒性T细胞的产生和体液免疫反应与其他形式的细胞免疫同时发展，类似于经典的迟发型或结核菌素样超敏反应，其本身可能是器官同种异体移植排斥中的一种强大效应机制。
