Characterization of gamma delta T cell effector/memory subsets based on CD27 and CD45R expression in response to Mycobacterium bovis infection

Authors: GUERRA-MAUPOME, MARIANA - Iowa State University; Palmer, Mitchell; WATERS, WILLIAM - Retired ARS Employee; MCGILL, JODI - Iowa State University

Submitted to: ImmunoHorizons
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2019
Publication Date: 6/5/2019
Citation: Guerra-Maupome, M., Palmer, M.V., Waters, W.R., Mcgill, J.L. 2019. Characterization of gamma delta T cell effector/memory subsets based on CD27 and CD45R expression in response to Mycobacterium bovis infection. ImmunoHorizons. 3(6):208-218. https://doi.org/10.4049/immunohorizons.1900032.
DOI: https://doi.org/10.4049/immunohorizons.1900032

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in Texas, New Mexico, Indiana, California, and South Dakota as well as recurrence of infection in Michigan demonstrate that the disease is far from eliminated from the United States. Improved techniques are needed for detection of infected cattle as well as improved control strategies (e.g., vaccines). To develop improved tests and vaccines, it is beneficial to first understand the nature of bovine immune responses to the pathogen. In this study, important cell types of cattle involved in the immune response to bovine tuberculosis were characterized in blood samples collected from infected animals. These cells were identified and characterized in terms of function. This basic information will be useful for development of improved tests and vaccines for the control of tuberculosis in cattle.

Technical Abstract: Tuberculosis (TB) remains a leading cause of death from infectious diseases worldwide. Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB) and zoonotic TB infection. Gamma/delta T cells are known to 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 gamma/delta T cells. To date, the impact of M. bovis infection on bovine gamma/delta T cells and their effector and memory differentiation remains unknown. In this study, we show for the first time that circulating gamma/delta T cells from M. bovis infected cattle can be differentiated based on the expression of CD27, which is indicative of their capacity to respond to virulent M. bovis infection: CD27+ gamma/delta T cells proliferated in response to M. bovis antigen and thus, may compose the adaptive gamma/delta T cells cell compartment in cattle. We further show that bovine M. bovis-specific gamma/delta T cells express surface markers characteristic of TCM cells (CD45R- CD27+CD62L+) and that M. bovis-specific CD4 and gamma/delta T cells both upregulate the expression of the tissue-homing receptors CXCR3 and CCR5 during infection. Our studies contribute significantly to our understanding of gamma/delta T cell differentiation during TB infection, and provide important insights into the link between phenotypic and functional subsets in the bovine. Accurate characterization of gamma/delta T cell effector and memory-like responses induced during mycobacterial infection will contribute to improved strategies for harnessing the gamma/delta T cell response in protection against TB for both humans and animals.