Pals S T, Gleichmann H, Gleichmann E
J Exp Med. 1984 Feb 1;159(2):508-23. doi: 10.1084/jem.159.2.508.
We studied the alloreactive properties of donor T cells obtained from F1 mice that had recovered from the allosuppression of acute graft-vs.-host disease (GVHD) and showed mild symptoms of chronic GVHD, i.e., so-called secondary chronic GVHD. To this end, we used (B10 x DBA/2)F1 mice that had been injected with 10(8) B10 spleen cells 100-150 d previously. Such GVHD F1 mice were repopulated by lympho-hematopoietic cells of donor (B10) origin, which exhibited split tolerance towards the host: Whereas F1-specific donor T helper (Th) cells as well as T cells proliferating in the mixed lymphocyte reaction were readily demonstrable, F1-specific T suppressor (Ts) and T killer (Tk) cells were not, or were hardly, detectable; responses against third-party alloantigens were normal. Upon adoptive transfer to nonirradiated secondary recipients, the B10 cells obtained from the repopulated GVH F1 mice induced F1-specific enlargement of the draining popliteal lymph node and enhancement of the IgG formation therein. B10 cells of the same kind were unable, however, to induce lethal GVHD upon transfer to 950 rad-irradiated secondary (B10 x DBA/2)F1 recipients. We conclude that alloactivated donor Ts/Tk cells disappear from the host at a relatively early stage of GVHD, i.e., at the end of acute GVHD , presumably because they are short-lived. By contrast, the longevity of alloactivated donor Th cells causes the symptoms of secondary chronic GVHD.
我们研究了从已从急性移植物抗宿主病(GVHD)的同种异体抑制中恢复并表现出慢性GVHD轻微症状(即所谓的继发性慢性GVHD)的F1小鼠获得的供体T细胞的同种异体反应特性。为此,我们使用了100 - 150天前注射了10⁸个B10脾细胞的(B10×DBA/2)F1小鼠。此类GVHD F1小鼠由供体(B10)来源的淋巴细胞造血细胞重新填充,这些细胞对宿主表现出分裂耐受性:虽然F1特异性供体T辅助(Th)细胞以及在混合淋巴细胞反应中增殖的T细胞很容易被检测到,但F1特异性T抑制(Ts)细胞和T杀伤(Tk)细胞未被检测到或很难被检测到;对第三方同种异体抗原的反应正常。将从重新填充的GVH F1小鼠获得的B10细胞过继转移到未受照射的二级受体后,诱导了引流腘窝淋巴结的F1特异性肿大并增强了其中IgG的形成。然而,同样的B10细胞转移到950拉德照射的二级(B10×DBA/2)F1受体后无法诱导致死性GVHD。我们得出结论,同种异体激活的供体Ts/Tk细胞在GVHD的相对早期阶段,即在急性GVHD末期从宿主体内消失,推测是因为它们寿命短暂。相比之下,同种异体激活的供体Th细胞的长寿导致了继发性慢性GVHD的症状。