Subject(s)
Antigens, CD7/immunology , Concanavalin A/immunology , T-Lymphocytes/immunology , Adult , Antigens, CD7/genetics , Cell Division , Cell Line , Female , Humans , Jurkat Cells , Ligands , Male , Mannose , Middle Aged , Receptors, Antigen, T-Cell/immunology , Receptors, Concanavalin A/immunology , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Structure-Activity RelationshipABSTRACT
CD7+CD34+ lymphohematopoietic progenitor cells in bone marrow are capable of differentiating into either lymphocytes or myeloid cells. The mechanism whereby these bipotent progenitor cells are regulated is not yet clear. In this study, we investigated the role CD7 may play in the development of bipotent cells using two myeloid progenitor cell lines, KG-1 and KG-1a, as models for such cells. Our data showed that cross-linking CD7 on KG-1 and KG-1a cells induced transcription, translation, and secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). Anti-CD7 antibody also augmented the colony formation by KG-1 cells. Protein synthesis in KG-1 cells also increased as a result of anti-CD7 stimulation. These phenomena could be blocked by anti-GM-CSF, and supported the notion that the secreted GM-CSF was the primary mediator of CD7 effects. Together, these findings suggest that the interaction between CD7 and its putative ligand may play an important role in hematopoietic development.
Subject(s)
Antigens, CD7/physiology , Granulocyte-Macrophage Colony-Stimulating Factor/physiology , Hematopoietic Stem Cells/cytology , Antibodies, Monoclonal/pharmacology , Antigens, CD7/immunology , Base Sequence , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Leukemia, Myeloid, Acute/pathology , Molecular Sequence Data , Muromonab-CD3/pharmacology , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Protein Biosynthesis , Transcription, GeneticABSTRACT
CD7 is a T cell-associated antigen which appears early in ontogeny and persists on circulating T cells. It appears to have a significant role in T cell development and function. The precise mechanism by which this molecule mediates its effect is not known. In this paper, we expressed the extracellular domain of CD7 in the baculovirus system and used this product to study the function CD7 might have in T cell activation. The recombinant protein was found to be structurally similar to the native CD7 and recognized by monoclonal and polyclonal antibodies to CD7. This protein inhibited T cell proliferation induced by anti-CD3/anti-CD7 costimulation. It also inhibited the augmentation effect of anti-CD7 on suboptimal PHA stimulation. However, it did not block T cell proliferation induced by optimal doses of PHA, staphylococcal entertoxin A or B. Interestingly, the recombinant protein inhibited antigenic- and alloantigenic-induced T cell proliferation. The latter finding strongly suggests that a ligand for CD7 exists and crosslinking CD7 by this ligand may be responsible for the costimulatory role it plays in T cell activation.
