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.
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
W A
WA
Noort
R
R
Benner
H F
HF
Savelkoul
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D005434:Flow Cytometry; D006087:Graft vs Host Reaction / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets; D013997:Time Factors
D000906:Antibodies; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens