Autologous T cells control B-chronic lymphocytic leukemia tumor progression in human -> mouse radiation chimera

B-chronic lymphocytic leukemia (B-CLL) is characterized by the clonal accum ulation of CD5(+) B cells, It has been suggested that CLL cells may be regu lated by inhibitory and growth-promoting signals exerted by autologous T ce lls. We have recently described a model for human B-CLL in which peripheral blood mononuclear cells (PBMCs) are transplanted into the peritoneal cavit y of lethally irradiated mice radioprotected with bone marrow from mice wit h severe combined immunodeficiency, In this model, adoptive transfer of low -stage PBMCs leads to marked engraftment of T cells or combined T and CLL c ell engraftment, whereas infusion of high-stage PBMCs leads to dominance of CLL cells with a miniscule level of T-cell engraftment. This mutual exclus ive pattern of engraftment indicated that T. cells might control the expans ion of tumor cells in the peritoneum of recipient BALB/c mice. In the prese nt study, we further investigated this question and we demonstrate that is vivo T-cell depletion, using OKT3 antibody, markedly enhances the engraftme nt of B-CLL cells from patients with early-stage disease. In mice receiving PBMCs from 11 donors with advanced stage disease, the results were more he terogeneous, In five patients the results were similar to those observed in early stage, whereas in two cases no CLL cell engraftment was found in the absence of T cells. The addition of purified T cells to PBMCs led to a sub stantial decrease of CLL engraftment in three advanced-stage cases. These r esults strengthen the working hypothesis that autologous T cells can active ly suppress the expansion of the pathological cells in human-->mouse radiat ion chimera. This effect is prominent in early-stage disease, whereas in ad vanced stage suppresive and/or stimulatory effects may occur in different p atients, The interaction of T cells with tumor cells and the potential of a utologous T cell/immune-therapy in CLL can be further explored in this mode l.