Askenase P W, Szczepanik M, Ptak M, Paliwal V, Ptak W
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
J Immunol. 1995 Apr 15;154(8):3644-53.
Our prior studies showed that gamma delta T cells were required to assist alpha beta T cells in the successful adoptive cell transfer of contact sensitivity (CS) responsiveness. These TCR-gamma delta+ regulatory T cells in immune spleen and lymph node were CD3+, CD4-, CD8+, nonantigen-specific, and non-MHC-restricted. In the current work, experiments were conducted to determine the mechanisms of how the gamma delta T cells were required to assist the alpha beta T cells in CS. We found that similar regulatory gamma delta T cells were in the spleen of normal mice, but not in the spleen of nude nor SCID mice, suggesting that the regulatory gamma delta T cells were present before immunization and required the thymus for differentiation, and also required rearrangements of gamma delta V gene segments. Treatment of cell transfer recipient mice with Bordetella pertussis (Bp), or with a low dose of cyclophosphamide (50 mg/kg), restored the ability of alpha beta+ gamma delta- T cells to transfer CS. This and other results suggested that Bp caused the CS-assisting gamma delta T cells to leave the lymphoid organs (such as the spleen) and enter the circulation, and only then to be able to assist the TCR-alpha beta+ CS-effector T cells. This effect needed the simultaneous i.v. injection of the CS-effector alpha beta T cells and the CS-assisting gamma delta T cells. The results also suggested that treatment with cyclophosphamide inactivated suppressor T cells in the recipients that acted to inhibit the alpha beta T cell transfer of CS, and thus that the CS-assisting gamma delta T cells acted by protecting the CS-effector alpha beta T cells from this endogenous suppression. This suppression of CS transfers also was eliminated by treatment of recipients with two different mAbs to determinants on suppressor T cells. In conclusion, we have described regulatory TCR-gamma delta+ CS-assisting/protecting T cells that are non-antigen-specific, non-MHC-restricted, CD3+, CD8+ gamma delta T cells that may assist adoptive transferring CS-effector alpha beta T cells by making these effector T cells resistant to suppressor T cells in the normal recipients.
我们先前的研究表明，在接触敏感性（CS）反应的成功过继性细胞转移中，γδ T细胞是协助αβ T细胞所必需的。免疫脾和淋巴结中的这些TCR-γδ⁺调节性T细胞为CD3⁺、CD4⁻、CD8⁺，是非抗原特异性的，且不受MHC限制。在当前的研究中，我们进行了实验以确定γδ T细胞协助αβ T细胞产生CS反应的机制。我们发现正常小鼠的脾脏中存在类似的调节性γδ T细胞，但裸鼠和SCID小鼠的脾脏中则没有，这表明调节性γδ T细胞在免疫前就已存在，其分化需要胸腺，并且还需要γδ V基因片段的重排。用百日咳博德特氏菌（Bp）或低剂量环磷酰胺（50 mg/kg）处理细胞转移受体小鼠，可恢复αβ⁺γδ⁻ T细胞转移CS的能力。这一结果以及其他结果表明，Bp促使协助CS的γδ T细胞离开淋巴器官（如脾脏）并进入循环，只有这样才能协助TCR-αβ⁺ CS效应T细胞。这一效应需要同时静脉注射CS效应αβ T细胞和协助CS的γδ T细胞。结果还表明，用环磷酰胺处理可使受体中的抑制性T细胞失活，这些抑制性T细胞会抑制CS的αβ T细胞转移，因此协助CS的γδ T细胞通过保护CS效应αβ T细胞免受这种内源性抑制而起作用。用两种针对抑制性T细胞上决定簇的不同单克隆抗体处理受体，也可消除CS转移的这种抑制作用。总之，我们描述了调节性TCR-γδ⁺ CS协助/保护T细胞，它们是非抗原特异性的、不受MHC限制的、CD3⁺、CD8⁺γδ T细胞，可能通过使这些效应T细胞对正常受体中的抑制性T细胞产生抗性来协助过继转移CS效应αβ T细胞。
