WC1(+) gammadelta T cells indirectly regulate chemokine production during mycobacterium bovis infection in SCID-bo mice.
Previous studies have suggested an important role for WC1 (+)gammadelta 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 gammadelta 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-1alpha, 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 (+)gammadelta 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 IFNgamma) 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(+)gammadelta TCR(+) cells up-regulate cytokines with direct regulatory effects on T cell and macrophage function and express effector molecules with critical roles in cytotoxicity.
Alvarez
A J
AJ
University of Texas Medical Branch, Galveston, TX, USA.
Endsley
J J
JJ
Werling
D
D
Mark Estes
D
D
D000818:Animals; D002417:Cattle; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D007150:Immunohistochemistry / Q000662:veterinary; D051379:Mice; D016513:Mice, SCID; D009163:Mycobacterium bovis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000097:blood / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000097:blood / Q000276:immunology* / Q000473:pathology
D018925:Chemokines; D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta