WC1+ gamma delta T cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis respond differentially to stimulation with PPD-J.

Authors: ALBARRAK, S - Iowa State University; HOSTETTER, J - Iowa State University; Waters, Wade; Stabel, Judith

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/7/2017
Publication Date: 7/14/2017
Citation: Albarrak, S., Hostetter, J., Waters, W.R., Stabel, J.R. 2017. WC1+ gamma delta T cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis respond differentially to stimulation with PPD-J. Veterinary Immunology and Immunopathology. 190:57-64. https://doi.org/10.1016/j.vetimm.2017.07.007.
DOI: https://doi.org/10.1016/j.vetimm.2017.07.007

Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle characterized by diarrhea, reduced feed intake, weight loss and death. Cattle usually become infected as young calves by ingesting feces containing the causative bacteria. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced milk production by these animals, they also present a potential infective threat to the rest of the herd. Little is known how the cow controls this infection in the early stages and what happens to allow full-blown disease to develop. This study presents information on the role of a specific group of T cells in cows in different stages of disease and how the responses of these cells differ between the stages of disease. This information helps us with understanding key events in the progression of disease from the early asymptomatic stage to more advanced clinical disease. Results suggest this group of T cells is part of a protective mechanism in animals in the early stage of infection. Understanding the host immune response to this pathogen will help us develop new therapeutic strategies as well as new diagnostic tools and vaccines to prevent the spread of disease.

Technical Abstract: A role for gamma delta T cells in protection against mycobacterial infections including Johne’s disease (JD) has been suggested. In neonatal calves where the risk to infection with Mycobacterium avium subsp. paratuberculosis (MAP) is high, the majority of circulating CD3+ lymphocytes are gamma delta TCR+. Bovine gamma delta T cells are divided into two major subsets based on the surface expression of workshop cluster 1 (WC1). The WC1+ subset, the predominant subset in periphery, is further divided into WC1.1+ and WC1.2+ subpopulations. The ability of gamma delta T cells to produce IFN-gamma prior to CD4+ alpha beta T cell activation could be crucial to the outcome of MAP infection. In the current study, cattle were naturally infected with MAP and were classified as either in the subclinical or clinical stage of infection. Compared to the control non-infected group, gamma delta T cell frequency in circulating lymphocytes was significantly lower in the clinical group. The observed decline in frequency was restricted to the WC1.2+ subset, and was not associated with preferential migration to infection sites (distal-ileum). Gamma delta T cells proliferated significantly in recall responses to stimulation with purified protein derivative from MAP (PPD-J) only in subclinically infected cattle. These responses were a heterogeneous mixture of WC1.1 and WC1.2 subsets. Proliferation and IFN-gamma production by the WC1.1+ gamma delta T cell subset was significantly higher in the subclinical group compared to the control and clinical groups. Our data provide evidence that WC1+ gamma delta T cells promote the effective Th1 response observed during the subclinical stage of JD.