The Journal of Immunology, Vol 155, Issue 9 4189-4198, Copyright © 1995 by American Association of Immunologists

ARTICLES

Gamma delta T cells in the pathobiology of murine acute graft-versus- host disease. Evidence that gamma delta T cells mediate natural killer- like cytotoxicity in the host and that elimination of these cells from donors significantly reduces mortality

CA Ellison, GC MacDonald, ES Rector and JG Gartner
Department of Immunology, University of Manitoba, Winnipeg, Canada.

NK-like cytotoxicity in F1-hybrid mice with acute GVH disease is mediated by donor-derived CD3+/CD4-/CD8- cells that can lyse both NK- sensitive YAC-1 target cells as well as NK-resistant targets such as BW1100 and P815. Our objective was to determine whether this activity is mediated by gamma delta TCR+ cells. We showed that NK-like cytotoxic activity in the spleen and lymph nodes of mice with acute GVH disease could be depleted by indirect complement-mediated lysis using an Ab against gamma delta TCR. When purified NK1.1+ spleen cells that had been positively selected on a magnetic cell separator were used as effector cells, we found that NK-like cytotoxicity was mediated only by gamma delta TCR+ cells, suggesting that cells with NK-like activity are gamma delta TCR+/NK1.1+. We showed by flow cytometry experiments that coexpression of NK1.1 and TCR-gamma delta occurred on a large proportion of large granular lymphocytes in the spleens of GVH mice, but was not detectable in normal control mice. In GVH mice, fewer than 10% of small agranular NK1.1+ lymphocytes coexpressed NK1.1+ and gamma delta TCR+. On the basis of this hypothesis, we postulate that graft- derived large granular lymphocytes develop the NK1.1+/gamma delta TCR+ phenotype during the reaction, and that these cells play a role in the pathogenesis of acute GVH disease. We performed experiments to determine whether depletion of gamma delta T cells from donor mice affected the outcome of lethal GVH disease and found that there was a significant reduction in mortality.

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