Roles of CD8+ and CD4+ cells on lethal graft-versus-host disease in nude mice.
Roles of CD8+ and CD4+ cells on lethal graft-versus-host disease (GVHD) were investigated. Injection of spleen cells from C57BL/6 (B6) female mice into (BALB/c x B6)F1 nu/nu female mice caused subacute lethal GVHD (survival: 10-50 days). Injection of anti-Lyt-2.2 (CD8) monoclonal antibody (mAb) on days zero, four and 14 into recipient mice prolonged their survival for at least the 200-day observation period. Injection of anti-L3T4 (CD4) mAb also prolonged survival of the mice for more than 70 days, but they eventually died by 150 days. Pretreatment of the donor B6 spleen cells with anti-Lyt-2.2 (CD8) mAb and complement (C) prevented the development of GVHD, and their pretreatment with anti-L3T4 (CD4) mAb and C markedly prolonged the survival of recipient mice. Injection of a mixture of donor spleen cells pretreated with anti-Lyt-2.2 (CD8) mAb and C and those pretreated with anti-L3T4 (CD4) mAb and C induced subacute lethal GVHD. Injection of anti-L3T4 (CD4) mAb, but not anti-Lyt-2.2 (CD8) mAb on days five, nine and 14 prolonged survival of the recipient mice. These results indicated that the collaboration of CD8+ cells and CD4+ cells was necessary for induction of subacute lethal GVHD. CD4+ cells but not CD8+ cells were involved in mediating subacute GVHD from the onset of the disease. CD8+ cells were, however, capable of inducing late-onset lethal GVHD. Direct phenotyping of T cells in the recipient mice revealed that the CD4+ cells were incapable of repopulating without CD8+ cells, but that CD8+ cells were capable of repopulating without CD4+ cells.
Uenaka
A
A
Department of Tumor Immunology, Center for Adult Diseases, Osaka, Japan.
Kuribayashi
K
K
Nakayama
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis*; D017690:Cell Transplantation / Q000009:adverse effects*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013154:Spleen / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens