Positive regulatory gamma delta T cells in contact sensitivity: augmented responses by in vivo treatment with anti-gamma delta monoclonal antibody, or anti-V gamma 5 or V delta 4.

Contact sensitivity (CS) responses, induced by skin painting with reactive haptens like picryl chloride or oxazolone, are classical examples of in vivo immunity mediated by alpha beta T cells. Our previous studies showed that gamma delta T cells were required to assist the alpha beta CS-effector T cells in the successful adoptive cell transfer of CS responses. These spleen and lymph node-derived gamma delta+ CS-assisting regulatory cells were CD3+, CD4-CD8+, non-antigen-specific, and non-MHC-restricted, and preferentially expressed V gamma 5 and V delta 4 variable regions. In the current study we show that systemic treatment of mice in vivo with anti-gamma delta mAb, produced a similar positive influence on CS responses in two different systems: i.e. active sensitization, or adoptive cell transfer. In addition to augmented CS responses produced by treatment with pan anti-gamma delta TCR mAb, anti-gamma delta-V region mAb were examined, and augmentation of CS also was produced by anti-V gamma 5 and anti-V delta 4 mAb, the V regions determined previously to be preferentially expressed on gamma delta CS-assisting cells. We speculate that the positive influence of anti-gamma delta mAb was not caused by quantitative changes in gamma delta T cells, because FACS studies demonstrated a lack of in vivo depletion of peripheral blood and lymphoid gamma delta T cells, and also no depletion of epidermal dendritic gamma delta T cells (DETC), in mice treated with anti-gamma delta TCR mAb. Instead, our data favor the hypothesis that CS-assisting gamma delta T cells can be activated in vivo by anti-gamma delta TCR mAb interacting with their gamma delta TCR, at least with the short term protocols we employed, resulting in augmentation of CS responses perhaps by releasing positively-acting factors, such as certain cytokines.