Role of T cell subsets in lethal graft-versus-host disease (GVHD) directed to class I versus class II H-2 differences. I. L3T4+ cells can either augment or retard GVHD elicited by Lyt-2+ cells in class I different hosts.
Detailed information was sought on the capacity of purified Lyt-2+ cells to mediate lethal graft-versus-host disease (GVHD) directed to class I H-2 differences. When B6 Lyt-2+ cells were transferred to irradiated class I-different (B6 x bm 1)F1 mice, three different patterns of lethal GVHD were observed. First, rapid death from hematopoietic failure occurred when Lyt-2+ cells were transferred together with host-type marrow cells; this form of GVHD probably reflected direct destruction of stem cells by Lyt-2+ cytotoxic cells. Second, a pattern of late-onset, chronic GVHD resulting in death only after 4-6 wk occurred when Lyt-2+ cells were supplemented with donor marrow. This syndrome developed in the apparent absence of L3T4+ cells and was observed with either high or low doses of Lyt-2+ cells and with either light or heavy irradiation of the host. Third, an acute form of GVHD resulted when Lyt-2+ cells plus donor marrow cells were supplemented with exogenous help, i.e., by adding small doses of donor L3T4+ cells or injecting the hosts with rIL-2. Although L3T4+ cells potentiated GVHD when injected in small doses, supplementing Lyt-2+ cells with large doses of L3T4+ cells paradoxically led to marked protection; symptoms of GVHD were mild and no deaths occurred.
Sprent
J
J
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Schaefer
M
M
Gao
E K
EK
Korngold
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D016026:Bone Marrow Transplantation; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013934:Thymectomy
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2