The role of bovine gamma delta T cells and their WC1 co-receptor in response to bacterial pathogens and promoting vaccine efficacy: A model for cattle and humans

Authors: BALDWIN, CYNTHIA - University Of Massachusetts; HSU, HAOTING - University Of Massachusetts; CHEN, CHUANG - University Of Massachusetts; Palmer, Mitchell; McGill, Jodi; Waters, Wade; TELFER, JANICE - University Of Massachusetts

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/21/2014
Publication Date: 6/15/2014
Publication URL: http://handle.nal.usda.gov/10113/58824
Citation: Baldwin, C.L., Hsu, H., Chen, C., Palmer, M.V., McGill, J.L., Waters, W.R., Telfer, J.C. 2014. The role of bovine gamma delta T cells and their WC1 co-receptor in response to bacterial pathogens and promoting vaccine efficacy: A model for cattle and humans. Veterinary Immunology and Immunopathology. 159(3-4):144-155.

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, an outbreak of tuberculosis in white-tailed deer in Michigan and continued importation of tuberculous cattle from Mexico have seriously hindered eradication efforts within the United States. Without new strategies, eradication and control of bovine tuberculosis will be impossible. Thus, improved techniques for control, such as better diagnostic tests and vaccines, are needed for prevention of tuberculosis in cattle. This article provides a summary on the current knowledge of a subset of bovine white blood cells and their role in infectious disease processes, including bovine tuberculosis, leptospirosis, and other important diseases of cattle. Knowledge presented in this article will be useful for the dissemination of information critical for the advancement of new strategies to be used in the United States and elsewhere for tuberculosis control.

Technical Abstract: Gamma deltaT cells are critical to immune surveillance and protection since they are found as resident cells in many organs and tissues, including in humans and ruminants, and circulate at substantial numbers in the blood. It is known that gamma delta T cells contribute to cellular immunity and protection against important pathogens including organizing granulomas in response to Mycobacteria. We have shown that IFN gamma-producing bovine gamma delta T cells bearing the WC1 co-receptor are the major cell population responding in recall responses to Leptospira during the first month following priming by vaccination against serovar Hardjo. To date, successful vaccines largely include those to diseases that only require antibody responses for protection and attempts at creating subunit peptide vaccines to stimulate conventional gamma delta T cells for cellular immune responses have been mostly unsuccessful. However, activation of non-conventional T cells, such as gamma delta T cells that direct adaptive T cell responses, has received little attention for improving vaccines because it is not clear how best to prime gamma delta T cells for recall responses. Annotation of the bovine genome showed there were 13 WC1 molecules coded for by individual genes. This gene number is conserved among breeds and individuals and expression of the WC1 molecules are distributed among cells to form a number of gamma delta T cell subsets. Using RNA silencing, we have shown that the WC1 co-receptor contributes to the ability of gamma delta T cells to respond to Leptospira spp. The Leptospira-responsive gamma delta T cells are found within a subset of the serologically defined WC1.1+ gamma deltaT cell subpopulation and our data indicate that the WC1 molecules expressed act as pattern recognition receptors inter-acting directly with bacterial components. We are now extending this work to Mycobacteria bovis.