Search results for: Mouse Anti-Bovine IL-12 Antibodies
#19486309 
2009/05/26
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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.A J Alvarez, J J Endsley, D Werling, D Mark Estes
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Natural killer cell-dependent immunoglobulin G2a anti-bovine serum albumin (BSA) response elicited by high molecular weight dextran-BSA conjugates associated with dextran-mediated macrophage-natural killer cell interaction.
The roles of the interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) produced during natural killer (NK) cell interaction with macrophages (M phi) were investigated as the basis for the induction of immunoglobulin G2a (IgG2a) anti-bovine serum albumin (BSA) responses by high molecular weight dextran conjugated to BSA (HMW-DEX-BSA). BALB/c mice immunized with HMW-DEX-BSA produced significantly higher levels of both IgG1 and IgG2a anti-BSA than did mice immunized with BSA alone. Both IgG1 and IgG2a anti-BSA levels were higher in mice immunized with BSA conjugated to dextran of molecular weight (MW) 5 000 000-40 000 000 compared with dextran of MW 10,000-60,000. The enhancement of anti-BSA IgG2a levels but not of anti-BSA IgG1 levels was inhibited when free BSA was added to the HMW-DEX-BSA conjugate. NK cell depletion during HMW-DEX-BSA immunization of mice resulted in significantly lower anti-BSA IgG2a levels without affecting anti-BSA IgG1 levels. Naive splenocytes or M phi + NK cell co-cultures incubated with HMW-DEX or HMW-DEX-BSA produced higher IFN-gamma levels than splenocytes or co-cultures incubated with BSA alone. HMW-DEX stimulated both IFN-gamma and IL-12 production by M phi + NK cell co-cultures in a dose-dependent manner. DEX-induced IFN-gamma production by NK cells was dependent upon the presence of IL-12, and IL-12 production by M phi was dependent upon the presence of IFN-gamma in these co-cultures. Both M phi and NK cells bound DEX to their surfaces. These data demonstrate that BSA linked to HMW-DEX enhanced both T-helper-1- and T-helper-2-associated antibody responses to BSA. The results also indicate an IL-12-dependent positive feedback interaction between NK cells and M phi that supports a NK cell/IFN-gamma-dependent mechanism for enhancement of anti-BSA IgG2a antibody responses in mice immunized with HMW-DEX-BSA protein conjugates.C P Ediriwickrema, S L Tonkonogy, B Hammerberg