Prevention of lethal graft‐vs.‐host disease by a single low dose injection of anti‐T cell monoclonal antibody to the allograft recipients

Abstract

We investigated the capacity of monoclonal antibody (mAb) treatment to prevent graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice, employing anti-T cell (subset) mAb and a fully allogeneic strain combination. In this strain combination, purified CD4+ cells were able to induce a lethal GVH reaction, whereas purified CD8+ cells were not. In the same strain combination, a single intraperitoneal injection of IgG2b anti-Thy-1 mAb, one day after reconstitution, caused a dose-dependent improvement of the survival. A single injection of a dose as low as 12.5 micrograms per mouse was already effective. Intravenous and intraperitoneal administration of the mAb appeared equally effective. For effective prevention of GVHD the treatment could be postponed until the 4th day after transplantation, but treatment delayed until day 6 was no longer effective. Treatment with IgG2b mAb specific for either helper or cytotoxic T cells also led to improvement of GVHD and survival, but was less effective than treatment with anti-Thy-1 mAb. Clinically, there was a difference in the effectiveness of anti-CD4 and anti-CD8 treatment, since symptoms of GVHD started earlier in the anti-CD8 treated group and the survival was better in the anti-CD4 treated group. These results press for prospective clinical studies employing anti-T cell mAb treatment early after allogeneic bone marrow transplantation, especially in HLA mismatched cases.

Modulation of systemic cytokine levels by implantation of alginate encapsulated cells

“…Cell suspensions were stained with anti-I-A ° (done 39-10-8, Pharmingen, San Diego, CA) mAb as described previously (Knulst et al, 1991). Cells were analysed using a flow cytofluorometer (FACScan, Becton Dickinson, Mountain View, CA).…”

Improved survival from potentially lethal graft‐vs.‐host disease by donor pretreatment with a recipient‐specific blood transfusion. II. Evidence for a principal role of the CD4+ T cell subset

“…We have earlier found that CD4+ T cells play a central role in the induction of lethal GVHD in this strain combination [6]. The fact that CD4+ Tcells from transfused donors caused reduced morbidity and mortality suggests that the pretreatment results in functional impairment of CD4+ Tcells.…”

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

“…We formerly demonstrated that in the fully allogeneic BALB/c-(C57BL x CBA)Fl strain combination transplantation of purified CD4+ T cells induced lethal GVHD, whereas purified CD8+ T cells did not, suggesting a major role for the CD4+ T cell subset. 2 Flow cytometric analysis of T cell subsets in the spleen of the (C57BL x CBA)Fl recipients early after reconstitution demonstrated a strong increase in the number of CD4' T cells peaking on day 4 or 5. Also the number of CD8+ T cells increased strongly, but consistently peaked l-2 days later.…”