Characterization of bovine γδ T cells phenotype during post-natal development and following Mycobacterium bovis vaccination or virulent infection

Abstract

Abstract Bovine tuberculosis caused by Mycobacterium bovis is a globally significant veterinary health problem. γδ T cells participate in the immune control of mycobacterial infections. Data in human and non-human primates suggest that mycobacterial infection regulates memory/effector phenotype and adaptive immune functions of mycobacterium-responsive γδ T cells. To date, the impact of age or M. bovis infection on bovine γδ T cells memory/effector phenotype remains unknown. In this study, we addressed the age-dependent changes of circulating γδ T cells, analyzed functional and phenotypic differences in memory and activation marker expression, and evaluated functional responses of M. bovis-specific γδ T cells following M. bovis Bacille Calmette-Guerin (BCG) vaccination or virulent M. bovis infection. As expected, aerosol vaccination and virulent infection induced robust mucosal and systemic M. bovis-specific γδ T cell proliferative responses. Analysis of peripheral blood γδ T cells indicated phenotypic differences based on the expression of CD27 and CD45R that could suggest distinct functional properties. Recall responses after in vitro stimulation with mycobacterial antigens showed that expression of CD27 is critical for the expansion of peripheral IFN-γ-producing γδ T-cells and suggest that the CD27+ subset may compose the mycobacterium-responsive γδ T cell compartment in calves responding to M. bovis vaccination or infection. The ability of γδ T cells to mount a robust response during mycobacterial infections supports the notion that vaccine-elicited γδ T cell immunity might prove beneficial. Therefore, defining correlates of protection based on this population can accelerate the development of novel vaccines against TB.