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WC1 + γδ T Cells Indirectly Regulate Chemokine Production During Mycobacterium bovis Infection in SCID‐bo Mice
Author(s) -
Alvarez A. J.,
Endsley J. J.,
Werling D.,
Mark Estes D.
Publication year - 2009
Publication title -
transboundary and emerging diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.392
H-Index - 63
eISSN - 1865-1682
pISSN - 1865-1674
DOI - 10.1111/j.1865-1682.2009.01081.x
Subject(s) - chemokine , splenocyte , interleukin 12 , mycobacterium bovis , cd3 , biology , ccl22 , immunology , isotype , spleen , cxcl10 , monoclonal antibody , microbiology and biotechnology , inflammation , antibody , antigen , medicine , cytotoxic t cell , cd8 , pathology , mycobacterium tuberculosis , tuberculosis , biochemistry , in vitro
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.