Gamma delta T cells in normal spleen assist immunized alpha beta T cells in the adoptive cell transfer of contact sensitivity. Effect of Bordetella pertussis, cyclophosphamide, and antibodies to determinants on suppressor cells.

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.