Submitted to: Journal of Interferon Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/1996
Publication Date: N/A
Interpretive Summary: Babesia bigemina and Babesia bovis are tick-transmitted protozoan parasites that cause severe morbidity and mortality in infected animals and humans. Babesia-derived rhoptry-associated proteins are being investigated for their ability to confer protection to cattle against this debilitating parasite genus; however, the mechanism of action of this class of proteins as it relates to host immune responses is not well understood. Furthermore, it is not known whether recombinant-derived antigens are eliciting the same host immune responses as the naturally- derived, protective parasite proteins. This work sought to investigate host cytokine responses that are associated with the protected state of the animal using newly-derived reagents for studying cytokine gene expression. Results are consistent with a class of host immune responses elicited by a recombinant rhoptry protein that are the same as that elicited by the naturally- derived protein. These results are important to the scientific community in that they demonstrate that the reagents developed at the USDA generate data consistent with what occurs in natural infections and further indicate that these reagents can be good predictors of host immune responses occurring under natural conditions.
Technical Abstract: Rhoptry-associated protein-1 (RAP-1) homologues of Babesia bigemina and B. bovis are promising candidates for inclusion in subunit vaccines against these hemoprotozoan parasites. Partial protection against challenge infection has been achieved with native forms of these antigens, but the mechanism of immunity has not been thoroughly defined. We previously demonstrated that a panel of antigen-specific T helper cell clones derived from B. bigemina RAP-1 immunized cattle expressed relatively high levels of interferon-y (IFN-g) protein and transcript, and low levels of interleukin-4 (IL-4), indicative of a type 1 immune response. In the current study we present evidence that subcutaneous immunization with native B. bigemina RAP-1 protein in RIBI adjuvant induces a predominant type 1 immune response in vivo, characterized by relatively high levels of IFN-y and IL-2 and low levels of IL-4 and IL-10 mRNA in the draining prescapular lymph node removed three days following the last antigen inoculation. Ex vivo restimulation of draining lymph node lymphocytes with specific antigen resulted in proliferation and enhanced expression of IL-2 and IFN-g, while IL-4 and IL-10 transcript levels remained relatively low. These findings show that our previously described cytokine profiles of antigen-specific cloned T cell lines are representative of autologous in vivo responses and confirm that type 1 recall responses to B. bigemina RAP-1 can be evoked in immunized animals by native parasite antigen.