Neutralization of bovine Concanavalin‐A T cell supernatant‐mediated anti‐Cowdria ruminantium activity with antibodies specific to Interferon gamma but not to tumor necrosis factor

Abstract

In an earlier study we demonstrated that Concanavalin-A stimulated bovine T cell supernatants inhibited the growth of Cowdria ruminantium in bovine endothelial cells in vitro. An investigation was conducted to identify the cytokines which were responsible for this growth inhibition. Addition of antiserum against bovine interferon gamma (IFN gamma) reproducibly neutralized the inhibitory effect of the T cell supernatants, whereas addition of antisera against bovine tumor necrosis factor alpha (TNF alpha) had no effect. The inhibitory effect of IFN gamma on C. ruminantium growth was not mediated by the production of nitric oxide as there was no detectable difference in nitric oxide levels in cultures that were supplemented with T cell supernatants compared with those that were not. The IFN gamma mediated anti-C. ruminantium effect highlights the importance of cell mediated immune responses in control of these infections and in particular incriminates the protective role of T cells, or cells that secrete IFN gamma.

Mechanisms of Immunity toEhrlichia muris: a Model of Monocytotropic Ehrlichiosis

“…In the present reported studies, the importance of CD8 and CD4 T lymphocytes, antibodies, and IFN-␥ combined with TNF-␣ in protective immunity of mice against E. muris was demonstrated for the first time. The data confirmed some principles previously proposed for immunity to ehrlichiae mediated by antibodies, Fc receptors, MHC class II, and IFN-␥ and suggest novel anti-ehrlichial mechanisms involving MHC class I and CTL (1,3,5,8,14,21,22,26,44,50).…”

“…Bovine endothelial cells activated by IFN-␥ inhibit the growth of intracellular E. ruminantium in association with the production of nitric oxide and without evidence for a role for TNF-␣ (26,27,30,44). Moreover, DBA/2 mice are protected against E. ruminantium by adoptive transfer of splenic T lymphocytes (which secrete a significant concentration of IFN-␥, but not TNF-␣, when stimulated by E. ruminantium antigens) (5).…”

Major Antigenic Proteins 1 and 2 of Cowdria ruminantium Are Targets for T‐Lymphocyte Responses of Immune Cattlea

“…Type 1 responses have been hypothesized to be required for protective immunity to C. ruminantium infection. It has been shown in previous studies that cytokines such as IFN‐γ inhibit the growth of C. ruminantium in bovine endothelial cells in vitro 5,6 and that animals which recover from the disease without treatment have higher plasma concentration of another cytokine, IFN‐α2. These observations have prompted the belief that development of new vaccine strategies for heartwater should focus on the immune responses that enhance production of C. ruminantium ‐inhibitory cytokines such as IFN‐γ and IFN‐α.…”

Ehrlichia

“…Numerous studies with E. ruminantium suggest that IFN-γ is an essential mediator in protection ( Totte et al, 1993( Totte et al, , 1996Mahan et al, 1994bMahan et al, , 1996Mutunga et al, 1998 ). IFN-γ production by CD4 ϩ and CD8 ϩ T cells in a protective response to E. ruminantium has been demonstrated ( Esteves et al, 2004a( Esteves et al, , 2004b.…”