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 et al., 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, The Journal of immunology, 155(9), 1995, pp. 4189-4198
NK-like cytotoxicity in F-1-hybrid mice with acute GVH disease is medi
ated by donor-derived CD3+/CD4(-)/CD8(-) cells that can lyse both NK-s
ensitive YAC-1 target cells as well as NK-resistant targets such as BW
1100 and P815. Our objective was to determine whether this activity is
mediated by gamma delta TCR(+) cells. We showed that NK-like cytotoxi
c activity in the spleen and lymph nodes of mice with acute GVH diseas
e 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 eff
ector cells, we found that NK-like cytotoxicity was mediated only by g
amma delta TCR(+) cells, suggesting that cells with NK-like activity a
re gamma delta TCR(+)/NK1.1(+). We showed by flow cytometry experiment
s that coexpression of NK1.1 and TCR-gamma delta occurred on a large p
roportion of large granular lymphocytes in the spleens of GVH mice, bu
t was not detectable in normal control mice. In GVH mice, fewer than 1
0% of small agranular NK1.1(+) lymphocytes coexpressed NK1.1(+) and ga
mma delta TCR(+). On the basis of this hypothesis, we postulate that g
raft-derived large granular lymphocytes develop the NK1.1(+)/gamma del
ta TCR(+) phenotype during the reaction, and that these cells play a r
ole 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.