Modulation of chronic lymphocytic leukemia (CLL) lymphocyte phenotypes by in vitro incubation with alpha 1 thymosin

In this study an attempt was made to elucidate (1) the level(s) of differentiation arrest of B cells, and (2) whether T-cell functional defects in CLL patients are related to their defective maturation. In addition, an attempt was also made to induce and/or correct maturation of T cells in CLL patients by in vitro incubation with alpha 1 thymosin. In CLL patients and controls, we determined the percentage of T and B cells with T11, T8, T4, C3, and mouse erythrocyte (ME) receptors, along with T-cell functional reactivity (measured by local xenogeneic graft vs host reaction), before and after incubation with alpha 1 thymosin. In about 60% of stable CLL patients, and in 80% of those in the progressive phase of disease, T cells possess receptors for ME and/or C3. After incubation with alpha 1 thymosin, separate analysis of surface markers on T and B cells revealed (along with the induction of T11 receptors on T-cell surface) induction of ME receptors on T and B cells in stable phase and selective loss of ME receptors on B cells in the progressive phase of CLL. After incubation of normal lymphocytes with alpha 1 thymosin, we observed an increase of T8 receptors, no change in expression of T11, and a decrease of T4 receptors along with the increase of the intensity of T-cell functional reactivity. In contrast, in CLL patients following incubation with alpha 1 thymosin, the induction of T8 receptors was less prominent in the progressive than in the stable phase of disease. Furthermore, induction of T8 receptors in CLL patients in the stable phase was accompanied by recovery of impaired or increase of preserved functional T-cell reactivity. In the progressive phase, however, T-cell functional areactivity remained unchanged. The findings suggest that different levels of B-cell-differentiation arrest along with defective maturation of T cells might be responsible for the spectrum of disease evolution in CLL.