Major histocompatibility complex-specific prolongation of murine skin and cardiac allograft survival after in vivo depletion of V beta+ T cells.
Major histocompatibility complex-specific prolongation of murine skin and cardiac allograft survival after in vivo depletion of V beta+ T cells.
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DOI：
10.1084/jem.177.1.35
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发表时间：
1993-01-01
期刊：
影响因子：
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通讯作者：
Hansen TH
中科院分区：
文献类型：
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作者：
Goss JA;Pyo R;Flye MW;Connolly JM;Hansen TH
在几种主要组织相容性复合体(MHC)限制性免疫反应中，某些T细胞受体(TCR)Vβ基因的优先使用已得到很好的证实。然而，Vβ在同种异体反应中的使用仍不清楚。因为我们和其他人最近的研究结果表明，Vβ8在某些LD限制性的、多肽特异的反应中占主导地位，所以我们研究了Vβ8在LD同种异体反应中的使用。为了选择性识别LD分子，用野生型BALB/c细胞体外或体内刺激LD缺失突变小鼠BALB/c-H-2dm2(DM2)细胞。在此，我们报道了用抗Vβ8单抗(MAb)F23.1经腹腔注射后，DM2小鼠外周血中Vβ8 T细胞被耗尽。体内的这种耗尽削弱了DM2脾细胞对LD分子产生主要反应的能力。这种去除是特异的，因为Vβ8耗竭的DM2细胞对KB/DB抗原的反应与对照未耗尽的DM2细胞相同。此外，体内Vβ8细胞的耗尽可导致不同于LD的皮肤移植物的显著延长(生理盐水对照组的平均存活时间[MST]22.1+/-2.1天对10.3+/-1.1天，或单抗KJ23至Vβ17组的10.9+/-1.7天)。相比之下，Vβ8缺失对移植了单倍型不匹配皮肤或单一DK基因不同皮肤的受者没有影响。这些发现表明，在LD的同种异体反应中，Vβ8+T细胞占主导地位，而其他同种异体抗原则不起作用。研究发现，Vβ8耗竭对接受异基因血管心脏移植的受者的影响更为显著(MST>；100天，对照组为8.6+/-0.5天)。总而言之，这些发现证实了使用针对Vβ基因家族的mAb来特异性和显著地提高同种异体移植物的存活率。文中还讨论了在同一I类分子的同种异体反应或MHC限制性TCR反应中检测Vβ8使用的意义。
The preferential usage of certain T cell receptor (TCR) V beta genes has been well established in several major histocompatibility complex (MHC)-restricted immune responses. However, V beta usage among allogeneic responses remains unclear. Because recent findings of ours and others indicate that V beta 8 predominates in certain Ld- restricted, peptide-specific responses, we examined the V beta 8 usage in allogeneic responses to Ld. To selectively recognize the Ld molecule, cells from BALB/c-H-2dm2 (dm2), the Ld-loss mutant mouse, were stimulated in vitro or in vivo with wild-type BALB/c cells. We report here that after the intraperitoneal administration of the anti-V beta 8 monoclonal antibody (mAb) F23.1, peripheral V beta 8 T cells were depleted from dm2 mice. This in vivo depletion abrogated the ability of dm2 splenocytes to mount a primary response to Ld molecules. This abrogation was specific, since the response of V beta 8-depleted dm2 cells to Kb/Db antigens was the same as that of control nondepleted dm2 cells. Furthermore, in vivo depletion of V beta 8 cells was found to cause a dramatic prolongation of Ld-disparate skin grafts (mean survival time [MST] 22.1 +/- 2.1 vs. 10.3 +/- 1.1 d for saline-treated controls, or 10.9 +/- 1.7 d for controls treated with mAb KJ23 to V beta 17). By contrast, V beta 8 depletion had no effect on recipients grafted with haplotype-mismatched skin or single Dk-locus-disparate skin. These findings demonstrate that V beta 8+ T cells predominate in allogeneic response to Ld but not other alloantigens. The effect of V beta 8 depletion was found to be even more dramatic on recipients grafted with Ld-disparate vascularized heart transplants (MST > 100 vs. 8.6 +/- 0.5 d for controls). In total, these findings establish the efficacy of using mAb to the V beta gene family to specifically and significantly enhance the survival of allografts. The implications of detecting V beta 8 usage in both alloreactive or MHC-restricted TCR responses to the same class I molecule are discussed.