Roles of CD8 + and CD4 + cells on lethal graft-versus-host disease in nude mice

Abstract

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 × B6)F 1 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.