So far as is known, all vertebrates contain two types of T-cells, an alpha/beta and a gamma/delta T-cell, distinguished by their alpha/beta and gamma/delta T-cell antigen receptors. The role of alpha/beta T-cells is reasonably well understood, but this is not the case for gamma/delta T-cells. Studies from many groups suggest that gamma/delta T-cells are quite different from alpha/beta T-cells in terms of antigen recognition and anatomical localization. But, there has been a longstanding need for a bioassay, by which to assess the function of gamma/delta T-cells and the effector mechanisms(s) that underlie it. In part, the problem has been the scarcity of gamma/delta T-cells, that in mice and humans are much less abundant than alpha/beta T-cells. To tackle these issues, the investigators' laboratory has developed mice that lack alpha/beta T-cells, and have challenged those, together with mice that lack gamma/delta T-cells with a natural protozoan parasite that targets the intestinal epithelium, a resident site of gamma/delta T-cells. The investigators found that the normal response of mice to this parasite is significantly affected by the deletion of either alpha/beta T-cells or gamma/delta T-cells, but in different ways. Whereas alpha/beta T-cells are essential for protection of the host, gamma/delta T-cell deficiency is associated with severe pathology. Thus the investigators believe that alpha/beta and gamma/delta T-cells indeed represent very different components of the immune system, and that an understanding of gamma/delta T-cell functions is therefore essential for our understanding of immune-related pathologies, particularly of the gut, e.g., inflammatory bowel disease. The bioassay for gamma/delta T-cells provided by the investigators' system should facilitate such an improved understanding. Both cellular and genetic approaches will be adopted. The investigators shall undertake the analysis of another bioassay for gamma/delta T-cells, for which the investigators have recently developed convincing evidence. In this assay, gamma/delta T-cells offer a significant level of anti-microbial protection without establishing immunity. Together the study of these assays may reveal why gamma/delta T-cells are so highly conserved.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Immunobiology Study Section (IMB)
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Hackett, Charles J
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Yale University
Schools of Arts and Sciences
New Haven
United States
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