No 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.

No abstract

Pretreatment of prospective donors of hemopoietic cells with a single recipient-specific blood transfusion can significantly decrease the morbidity and mortality of graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice. This beneficial effect of donor pretreatment could be demonstrated in donor-recipient strain combinations that were H-2 + non-H-2, H-2, or only class II-disparate, but not in the class I-disparate C57BL-B6.C-H-2bm1 strain combination. The effect was proportional to the amount of recipient-strain blood used for transfusion. Donor transfusion with a single dose of 1 ml recipient-specific whole blood resulted in minimum GVHD, lower doses being less or not effective. The interval between donor pretreatment and the use of their hemopoietic cells for reconstitution appeared to be important. The best survival was found at an interval of 4 days. Multiple transfusion was not more effective than a single one. We compared the effectiveness of whole blood and irradiated spleen cells for donor pretreatment. Both protocols have been shown previously to suppress anti-recipient delayed-type hypersensitivity. It appeared that the blood transfusion protocol was superior to the spleen cell protocol. The beneficial effect appeared to be recipient specific, since a third-party blood transfusion did not improve GVHD. We found that the beneficial effect of donor blood transfusion was due to suppression of the anti-host immune response. The donor blood transfusion was able to induce bystander suppression to alloantigens that were not used for the induction of suppression, provided they were co-expressed with the specific alloantigens by the recipients. This also indicates that, although the induction of suppression is specific, the ultimate suppressive effect is non-specific.

Graft‐versus‐host disease (GVHD) is caused by donor T lymphocytes that recognize foreign antigens on host tissues. This leads to T cell activation, which involves a cascade of events including the transcription of genes for cytokines and their receptors and the production of cytokines [1, 2]. One of the first cytokines to appear is interleukin 2 (IL‐2). IL‐2 production enhances the IL‐2 receptor expression and leads to T cell proliferation. As a further step, differentation of T cells occurs, which results in the production of a certain pattern of cytokines. These cytokines influence the expression of cell surface antigens and adhesion molecules, and are able to activate other cell types such as cytotoxic T cells, macrophages and natural killer cells, which might act as effector cells in tissue destruction [2]. Insight into the sequential expression of the various cytokines involved might enable a more effective treatment of GVHD. Therefore, we investigated the occurrence of cytokines in a murine model for acute GVHD. We addressed in particular the period early after allogeneic reconstitution.