WC1⁺γδ; T cells indirectly regulate chemokine production during mycobacterium bovis Infection in SCID-bo mice

Summary Previous studies have suggested an important role for WC1 ⁺γδ; T cells in the regulation of mycobacterial-induced inflammation in the spleen and liver of heterochimeric SCID-bovine (SCID-bo) mice. To examine the role of these cells, we investigated the levels of selected chemokines and IL12-p70 post-infection in reconstituted SCID-bo mice. Mice were treated with a monoclonal antibody specific for boWC1 to eliminate WC1-bearing cells. Isotype control treated or bovine γδ; TCR-depleted mice were assayed in parallel. Following infection with Mycobacterium bovis, mice were examined post-infection for the expression of IL12-p70, IP-10, MIP-1α, lymphotactin and MIG by ELISA in plasma and from activated splenocytes. Treatment with the anti-bovine WC1 resulted in reduced serum plasma levels of IP-10, MCP-1, and IL-12p70 versus control mice. The potential of WC1 ⁺γδ; TCR-bearing cells to produce chemokines and cytokines was determined directly from peripheral blood of cattle. Our results indicate that these cells have a fairly restricted capability to produce the chemokines examined in SCID-bo mice, but may be a significant source of cytokines (IL-2, IL-10, IL-12, IL-15, and IFNγ) and contribute to cytotoxicity through expression of FasL and perforin. In M.bovis-infected liver tissue, depletion of the WC1⁺ subset was associated with increased numbers of CD3⁺T cells adjacent to venules and portal tracts. These results suggest that the WC1⁺ subset in cattle may contribute to chemotaxis through indirect effects on chemokine levels. Further, activated WC1⁺γδ; TCR⁺ cells up-regulate cytokines with direct regulatory effects on T cell and macrophage function and express effector molecules with critical roles in cytotoxicity.