Evidence has been accumulating that cell membrane glycosphingolipids may serve as receptors for several biologically active agents including glycoprotein hormones, lymphokines and interferon and may play a role in cell activation. Using purified antibodies to aGM1, it has been demonstrated that this glycosphingolipid is expressed predominantly by cells in the T-lymphocyte lineage. The expression of aGM1 seems to be associated with functionally responsive status within the lineage. The aGM1 is expressed throughout the lineage and is exposed, masked, and re-exposed at certain stages of maturation and activation. We have demonstrated that a proportion of the multipotential hematopoietic stem cells (CFU-S) also expresses aGM1. The aGM1-positive CFU-S display a reduced self-renewal potential and are depleted in athymic mice. In the context of current theories of hematopoiesis, decreased self-renewal is associated with increased cell cycle activity and propensity to differentiate into committed progenitors. Thus the aGM1-positive CFU-S may represent mobilized stem cells, a subset of thymic dependent stem cells, or both. To attempt to resolve these questions, we propose to determine if aGM1 phenotype is associated with cell cycle activity of CFU-S and to determine if there is a difference in T cell dependency for self-renewal and differentiation of stem cell subpopulations defined by aGM1 phenotype. These studies will elucidate the bases for hematopoietic commitment and regulation at the stem cell level and thus provide a basis for studies on the mechanism of hematopoietic dysfunction in congenital, age-related and transplantation-related syndromes.
| Stout, R D; Suttles, J (1992) T cells bearing the CD44hi ""memory"" phenotype display characteristics of activated cells in G1 stage of cell cycle. Cell Immunol 141:433-43 |
| Stout, R D; Bottomly, K (1989) Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages. J Immunol 142:760-5 |
| Stout, R D; Suttles, J (1988) Problems and applications of cell cycle analysis: distinguishing G0 from G1 and G1 from S phase. Cytometry Suppl 3:34-7 |
| Suttles, J; Schwarting, G A; Stout, R D (1986) Flow cytometric analysis reveals the presence of asialo GM1 on the surface membrane of alloimmune cytotoxic T lymphocytes. J Immunol 136:1586-91 |
