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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #302873
Title: ZAP-70, CTLA-4 and proximal T cell receptor signaling in cows infected with Mycobacterium avium subsp. paratuberculosis

Author
item LEITE, FERNANDO - Iowa State University
item ESLABAO, LIVIA - Federal University - Brazil
item Pesch, Bruce
item Bannantine, John
item Reinhardt, Timothy
item Stabel, Judith

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/12/2014
Publication Date: 6/22/2014
Citation: Leite, F.L., Eslabao, L.B., Pesch, B.A., Bannantine, J.P., Reinhardt, T.A., Stabel, J.R. 2014. ZAP-70, CTLA-4 and proximal T cell receptor signaling in cows infected with Mycobacterium avium subsp. paratuberculosis [abstract]. International Colloquium on Paratuberculosis. p. 144.

Interpretive Summary:

Technical Abstract: Paratuberculosis is a chronic intestinal disease of ruminant animals caused by Mycobacterium avium subsp. paratuberculosis (MAP). A hallmark of paratuberculosis is a transition from a cell-mediated Th1 type response to a humoral Th2 response with the progression of disease from a subclinical to clinical state. The objective of this study was to investigate the expression of two crucial molecules in T cell function, ZAP-70 (zeta-chain associated protein of 70 kDa) and CTLA-4 (cytotoxic T-lymphocyte antigen-4), in cows naturally infected with MAP. Peripheral blood mononuclear cells (PBMCs) isolated from control non-infected cows (n=5), and cows in clinical (n=6) and subclinical stages of paratuberculosis (n=6) were cultured alone (medium only), with concanavalin A, and a whole cell sonicate of MAP for 24,72 and 144 hours to measure the dynamic changes of ZAP-70 and CTLA-4 expression on CD4, CD8, and gamma delta T cells. Flow cytometry was also performed to measure ZAP-70 phosphorylation to examine proximal T cell receptor signaling in animals of different disease status. It was found that the surface expression of CTLA-4 is dramatically increased in animals in subclinical stage of infection while levels of ZAP-70 are significantly decreased in CD4+ T cells of both subclinical and clinical animals, indicating a change in T cell phenotype with disease state. Interestingly, proximal T cell receptor signaling was not altered in infected animals. This study demonstrates changes in crucial signaling molecules in animals infected with MAP elucidating T cell alterations that are associated with disease progression.