Interferon-γ-mediated prevention of graft-versus-host disease: development of immune competent and allo-tolerant T cells in chimeric mice

Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice.

“…Previous studies have found that systemic administration of IFN-␥ can prevent GVHD, although the model used in those studies was more delayed with regard to onset than ours (18,19). Additionally, in those reports it was postulated that exogenous IFN-␥ administration worked by lowering endogenous production, suggesting that IFN-␥ is actually deleterious in GVHD (19). The data shown here would argue for a more direct role for the suppressive activities of IFN-␥, as there is no (20).…”

“…This is now confirmed by us with regard to alloantigen reactions in vivo. Previous studies have found that systemic administration of IFN-␥ can prevent GVHD, although the model used in those studies was more delayed with regard to onset than ours (18,19). Additionally, in those reports it was postulated that exogenous IFN-␥ administration worked by lowering endogenous production, suggesting that IFN-␥ is actually deleterious in GVHD (19).…”

IFN-γ-mediated prevention of graft-versus-host disease: pharmacodynamic studies and influence on proliferative capacity of chimeric spleen cells

“…Sykes and co-workers 25,26 demonstrated the association of GVHD with a peak production of IFN-␥ at days 4-5, which is in accordance with our own findings of an IFN-␥ peak at days 7-10 post BMT. 20,27 It was concluded that the protective effect of IL-2 was independent of NK cell or LAK cell activity 22 and based on the selective suppression of CD4 ϩ Th 1 -like cells 23,25 after the first week following BMT. Sykes and co-workers observed in their studies with IL-2 an expansion of a CD3 ϩ CD4 Ϫ CD8 Ϫ cell population at days 3-4 after BMT.…”

“…Similar suppression of proliferation of SC has been described by others after administration of IL-2 [23][24][25] or IL-12. 26 It was essential in all these 'cytokine-based' models that treatment had to be started at BMT in order to obtain the maximal protective effect [20][21][22][23][24][25][26][27] (Figure 3). The administration of IFN-␥ from day 2 onwards had no effect, as shown by Szebeni,25 which is in accordance with the findings in this study.…”

“…We have demonstrated that treatment with IFN-␥ prevented GVHD in a fully H-2-mismatched BMT mouse model. 20,27 Here we report on pharmacodynamic studies carried out to determine the most effective treatment schedule and to find the optimal dose of IFN-␥. The possible effect of IFN-␥ on T cells of donor origin present in the host was studied by testing the proliferative capacity of spleen cells (SC) shortly after BMT.…”