Anne G. Leary

Humoral Regulation of Stem Cell Proliferation

The central feature of hematopoiesis is life-long, stable cell renewal. This process is supported by hemopoietic stem cells which, in the steady state, appear to be dormant in cell cycling. The recruitment of the dormant stem cells into cell cycle may be promoted by such factors as interleukin (IL)-1, IL-6, granulocyte-colony stimulating factor (G-CSF), and newly discovered IL-11. The effects of IL-1 on stem cells may be indirect. Once the stem cells leave Go and begin proliferation, the subsequent process is characterized by continued proliferation and differentiation. Though several models of stem cell differentiation have been proposed, micromanipulation studies of individual progenitors suggest that the commitment of multipotential progenitors to single lineages is a stochastic process. The proliferation of early hemopoietic progenitors requires the presence of IL-3 and/or IL-4, and the intermediate process appears to be supported by granulocyte/macrophage-CSF (GM-CSF). Once the progenitors are committed to individual lineages, the subsequent maturation process appears to be supported by late-acting, lineage-specific factors such as erythropoietin (erythropoiesis), G-CSF (neutrophil production), and IL-5 (eosinophilopoiesis). Thus, hemopoietic proliferation appears to be regulated by a cascade of factors directed at different developmental stages.

Cell-Mediated Immunity in the Uremic Rat

The popliteal node assay of the graft-versus-host reaction in the inbred rat provides a sensitive measure of cell-mediated immunity. Spleen cells from uremic Lewis rats as well as normal cells cultured in uremic serum demonstrated significant immunosuppression which was proportional to the severity of the uremia.

Effect of cis-platinum(II)diamminedichloride and gallium nitrate on the ability of spleen cells to induce a graft-versus-host reaction.

Summary We used the recently described rat popliteal node assay, a sensitive in vivo test of thymic-dependent lymphocyte funciton, to measure the effects of cis-platinum (II) diamminedichloride and gallium nitrate on the ability of spleen cells from treated parental rats to induce a graft-versus-host reaction in hybrid recipients. In doses sufficient to cause morbidity and weight loss of the donor rats, no significant suppression of the reaction could be demonstrated.