Role of T cell subsets in lethal graft-versus-host disease (GVHD) directed to class I versus class II H-2 differences. II. Protective effects of L3T4+ cells in anti-class II GVHD.
Detailed information was sought on the capacity of purified B6 L3T4+ cells to elicit lethal graft-versus-host disease (GVHD) in irradiated class II-different class I-identical (C57BL/6 (B6) x bm 12)F1 hosts. When B6 L3T4+ cells were transferred in small doses (10(5) to 10(6) together with donor bone marrow (BM) cells, the recipients all developed acute lethal GVHD and most of the mice died within 2 wk, probably from gut damage; this syndrome was conspicuous only in mice treated with very heavy irradiation, i.e., 1000 rad. In marked contrast to L3T4+ cells given in small doses, transfer of large doses of B6 L3T4+ cells to heavily irradiated (B6 x bm 12)F1 hosts paradoxically resulted in only limited mortality: most of the recipients survived for greater than 6 mo and manifested little or no evidence of ill health. It is suggested that the capacity of large doses of L3T4+ cells to protect mice against lethal GVHD is a reflection of T helper function: the cellular immunity provided by the donor L3T4+ cells enables the host to repel pathogens entering through damaged mucosal surfaces, with the result that GVHD becomes sublethal. The protective function of L3T4+ cells in the B6----bm 12 combination was only seen in hosts given donor BM. With transfer of donor L3T4+ cells plus host BM, even lightly irradiated recipients died rapidly from hemopoietic failure. Because this syndrome failed to occur in mice given a mixture of donor and host BM, it would appear that L3T4+ cells destroyed host lymphohemopoietic cells by direct cytotoxicity rather than via a bystander effect.
Sprent
J
J
Department of Immunology, IMM4A Research Institute of Scripps Clinic, La Jolla, CA 92037.
Schaefer
M
M
Korngold
R
R
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004307:Dose-Response Relationship, Radiation; D006086:Graft vs Host Disease / Q000276:immunology*; D006410:Hematopoiesis; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D007410:Intestinal Diseases / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011828:Radiation Chimera
D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II