Positive Regulatory γδ T Cells in Contact Sensitivity: Augmented Responses by in Vivo Treatment with Anti-γδ Monoclonal Antibody, or Anti-Vγ5 or Vδ4

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Abstract
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 αβ T cells. Our previous studies showed that γδ T cells were required to assist the αβ CS-effector T cells in the successful adoptive cell transfer of CS responses. These spleen and lymph node-derived γδ+ CS-assisting regulatory cells were CD3+, CD4-CD8+, non-antigen-specific, and non-MHC-restricted, and preferentially expressed Vγ5 and Vδ4 variable regions. In the current study we show that systemic treatment of mice in vivo with anti-γδ 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-γδ TCR mAb, anti-γδ-V region mAb were examined, and augmentation of CS also was produced by anti-Vγ5 and anti-Vδ4 mAb, the V regions determined previously to be preferentially expressed on γδ CS-assisting cells. We speculate that the positive influence of anti-γδ mAb was not caused by quantitative changes in γδ T cells, because FACS studies demonstrated a lack of in vivo depletion of peripheral blood and lymphoid γδ T cells, and also no depletion of epidermal dendritic γδ T cells (DETC), in mice treated with anti-γδ TCR mAb. Instead, our data favor the hypothesis that CS-assisting γδ T cells can be activated in vivo by anti-γδ TCR mAb interacting with their γδ 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.