Differential effectiveness of anti-CD8 treatment on ongoing graft-versus-host reactions in mice.

Analysis of T cell subsets in the spleen during graft-versus-host (GVH) reactions in a fully allogeneic mouse strain combination demonstrated that first CD4+ T cells become activated, and initiate the GVH reaction. Subsequently, CD8+ T cells become involved. Here we show that anti-CD8 treatment on day +3 resulted in a significant increase in survival, while early treatment (day -1 or day +1) did not. Acute GVH reactions were induced (day 0) in lethally irradiated (C57BL/6 x CBA/J)F1 (H-2b/k) mice by intravenous injection of BALB/c (H-2d) spleen and lymph node cells (3.6 x 10(7)) within 24 h after irradiation. Mice were treated intraperitoneally with a single optimally depleting dose of rat anti-CD8 (YTS 169.4) or untreated. Symptoms of GVHD became obvious 6 days after reconstitution, and mortality started at day 8. The mutual influence of CD4+ and CD8+ T cells in the development of GVHD becomes apparent from our data, and demonstrates that GVHD lethality can be caused by CD8+ T cells as well as by CD4+ T cells.