Predominance of NK1.1(+)TCR alpha beta(+) or DX5(+)TCR alpha beta(+) T cells in mice conditioned with fractionated lymphoid irradiation protects against graft-versus-host disease: "Natural suppressor" cells

We developed a nonmyeloablative host conditioning regimen in a mouse model of MHC-mismatched bone marrow transplantation that not only reduces radiati on toxicity, but also protects against graft-vs-host disease. The regimen o f fractionated irradiation directed to the lymphoid tissues and depletive a nti-T cell Abs results in a marked change in the residual host T cells, suc h that NK1.1(+) or DX5(+)asialo-GM1(+) T cells become the predominant T cel l subset in the lymphoid tissues of C57BL/6 and BALB/c mice, respectively. The latter "natural suppressor" T cells protect hosts from graft-vs-host di sease after the infusion of allogeneic bone marrow and peripheral blood cel ls that ordinarily kill hosts conditioned with sublethal or lethal total bo dy irradiation. Protected hosts become stable mixed chimeras, but fail to s how the early expansion and infiltration of donor T cells in the gut, liver , and blood associated with host tissue injury. Cytokine secretion and adop tive transfer studies using wild-type and IL-4(-/-) mice showed that protec tion afforded by NK1.1(+) and DX5(+) asialo-GM1(+) T cells derived from eit her donors or hosts conditioned with lymphoid irradiation is dependent on t heir secretion of high levels of IL-4.