Autoimmune Manifestations Following autoBMT

In 1979, Rappaport et al. [33] described a syndrome of acute graft versus host disease in recipients of syngeneic bone marrow. Subsequently syngeneic GVHD induced by administration of a short course of low dose CSA was reported in rats [34, 35], A similar occurrence of syngeneic GVHD was also reported in mice [36]. Apparently, induction of syngeneic GVHD in mice may be more difficult to accomplish because other investigators failed to reproduce these results in mice despite repeated efforts [37], Spontaneous autologous GVHD was also described in man [38-40]. All of the above suggest that under normal circumstances immunoregulatory mechanisms may play an important role in controlling antiself-responses during the ontogeny of T-cell repertoire in the adult host following transplantation of autologous stem cells. The feasibility of induction of autologous GVHD and the existing data in support of direct relationship between GVHD and GVL brought hope that autologous GVHD may be useful for induction of GVL. Indeed, recently, autologous GVHD induced by CSA has been employed in an attempt to control residual disease following autoBMT [41,42] but no objective conclusions or direct measurements possible regarding antileukemic effects and improvement in disease free survival have been reported. Clinical manifestations indistinguishable from GVHD by clinical and pathologic parameters in patients undergoing syngeneic or even autoBMT suggests that imbalance of the reconstituting immune system resulting in antiself-responses may be further exploited in attempt to induce similar GVL or graft vs tumor (GVT) effects in conjunction with minimal residual disease induced by high-dose chemoradiotherapy. Unfortunately, in our own experiments in mice inoculated with murine B-cell leukemia, we failed to show any measurable GVL effects [43], However, in principle, antitumor responses may be elicited even against weakly immunogenic tumor cells, similarly to antiself-reactivity in autoimmune diseases. Since GVHD correlates with GVL following alloBMT, it remains to be seen whether the untoward autoimmune-like GVHD observed after autologous or syngeneic BMT can be translated to beneficial GVL effects. In this regards, our data suggest that it is not the GVHD per se that induces GVL, but rather donor T cells that can recognize residual tumor cells in the host as alloantigens can be effective in inducing GVL.

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