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

Abstract

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.

Immunity to Pre-1950 H1N1 Influenza Viruses Confers Cross-Protection against the Pandemic Swine-Origin 2009 A (H1N1) Influenza Virus

“…To deplete CD8 T cells in vivo, we used a rat IgG 2a anti-mouse CD8 mAb produced from the hybridoma, YTS169.4 (19). We administered the mAb i.p.…”

Characterization of in vitro antimurine thymocyte globulin–induced regulatory T cells that inhibit graft-versus-host disease in vivo

“…At 1 week following disease induction, there was a dramatic decrease in CD8 ϩ T-cell percentages in mice given mATG-treated splenocytes compared with mice given rabbit IgG splenocytes ( Figure 6D) that remained low throughout the disease course (data not shown). Because cytotoxic CD8 ϩ T cells are important for the direct tissue damage and acute manifestations of GVHD under conditions of disparities in both MHC class I and II loci, 44,45 the depletion of or suppression of the expansion and/or activity of CD8 ϩ T cells is beneficial in reducing disease symptoms. [44][45][46] These data indicate that the transfer of in vitro mATG-treated cells results in inhibition of allogeneic CD8 ϩ T-cell expansion.…”

“…Because cytotoxic CD8 ϩ T cells are important for the direct tissue damage and acute manifestations of GVHD under conditions of disparities in both MHC class I and II loci, 44,45 the depletion of or suppression of the expansion and/or activity of CD8 ϩ T cells is beneficial in reducing disease symptoms. [44][45][46] These data indicate that the transfer of in vitro mATG-treated cells results in inhibition of allogeneic CD8 ϩ T-cell expansion. There were no detectable effects of the mATG-treated splenocytes on CD4 ϩ T-cell percentages in the blood at any time point, however, it remains possible that depressed functional activity of CD4 T cells is responsible for limiting the CD8 ϩ T-cell expansion and decreased disease manifes- Figure 6.…”