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

gamma delta T 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 alpha beta 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 delta T cell subpopulation and our data indicate that the WC1 molecules expressed act as pattern recognition receptors interacting directly with bacterial components. We are now extending this work to Mycobacteria bovis. (C) 2014 Elsevier B.V. All rights reserved.