title: Control of helper-T-cell proliferation by recognition of Ia and Mac-1 antigens on phagocytic cells of the thymic reticulum.
abstract: Phagocytic cells of the thymic reticulum (P-TR) have been previously described as being Ia-positive, Mac-1-positive accessory cells which pursue a close relationship with thymocytes. They form rosettes with thymocytes, and these rosettes are inhibited by antibody directed against the complement receptor type 3 CR3 (anti-Mac-1). P-TR induce the proliferation of syngeneic thymocytes. In the present paper, we show that thymocytes enriched in mature medullary type are induced to proliferate in coculture with syngeneic P-TR, while the cortical type does not. After 5 days of culture, 85% of the thymocytes are of helper L3T4+Lyt-2- phenotype. As previously shown by others for syngeneic reactions, antibodies directed against related class II antigens (anti-I-A and anti-I-E) block this helper-T-cell syngeneic proliferation. A new finding is the blockage of helper-T-cell proliferation by anti-Mac-1 as well as with anti-LFA-1 antibodies, showing that accessory molecules may be as important as specific recognition of class II antigen molecules in the control of thymocyte proliferation and hence in thymocyte selection. Mac-1, like LFA-1, belongs to a novel family of differentiation antigens involved in cell interactions. The blockage of cell recognition and interaction between P-TR and thymocytes by either anti-Ia or anti-Mac-1 during the early induction phase of the syngeneic response leads to its inhibition. We demonstrate that P-TR/thymocyte interaction stimulates the enhanced expression of IL-2 receptors on thymocytes, a step which is necessary for helper-T-cell proliferation. The mechanism of syngeneic proliferation inhibition by anti-Ia, anti-Mac-1, and LFA-1 antibodies may be the prevention of IL-2 receptor expression on thymocytes, and/or the inhibition of IL-2 secretion. Although this is an in vitro model, which may not totally reflect in situ situation, our results indicate that thymic accessory cells may participate in a positive selection process which leads to helper-T-cell proliferation.
authors.affiliation: Inserm U 25, Hôpital Necker, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Papiernik
authors.forename: S
authors.initials: S
authors.lastname: el Rouby
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen; D051379:Mice; D008811:Mice, Inbred DBA; D008954:Models, Biological; D010586:Phagocytes / Q000276:immunology*; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen