title: Monocyte-dependent regulation of T lymphocyte activation through CD98.
abstract: CD98 is a 125 kDa heterodimer, which is strongly expressed on the surface of activated and proliferating cells. Its expression is strikingly regulated during T cell differentiation and activation, but the role of CD98 during T lymphocyte responses is not yet understood. We report here that proliferation of resting peripheral blood mononuclear cells (PBMC) induced by lectin, superantigen (SAg) or conventional antigens was blocked by anti-CD98 heavy chain (CD98hc) mAb. In contrast, anti-CD98hc did not block responses of T cell clones or lines. Anti-CD98hc inhibited IL-2 receptor expression and progression of T cells from G1 to S phase, but did not reduce expression of the IL-2 gene. Anti-CD98hc mAb did not regulate the initial activation events involving the TCR and co-receptor structures, but instead inhibited T lymphocyte responses even when added 18 h or more after the activation stimulus. Further experiments demonstrated that anti-CD98 was not directly affecting T cells in this system, but was instead acting on accessory cells. This was supported using a novel xenogeneic system that takes advantage of the lack of xenoreactivity of purified human T cells against mouse splenocytes. Despite absence of a direct xenoresponse to murine spleen cells, human T cells were activated by SAg presented by murine splenic antigen-presenting cells (APC). Murine anti-human CD98hc did not block T cell proliferation in this system. Furthermore, responses using monocyte-depleted PBMC as APC were not blocked by anti-CD98hc. Taken together, the present data suggests that triggering of human monocyte CD98 can suppress T cell proliferation by a process that halts progression through the cell cycle of recently activated T lymphocytes. This may represent a novel pathway for monocyte regulation of T cell activation.
authors.affiliation: Rackham Arthritis Research Unit, Department of Internal Medicine, Specialized Center of Research in Rheumatoid Arthritis, Ann Arbor, MI, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Diaz
authors.forename: A W
authors.initials: AW
authors.lastname: Friedman
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: R D
authors.initials: RD
authors.lastname: Kuick
authors.forename: S M
authors.initials: SM
authors.lastname: Hanash
authors.forename: D A
authors.initials: DA
authors.lastname: Fox
mesh_terms: D019138:Antibodies, Blocking / Q000187:drug effects / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology* / Q000502:physiology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology* / Q000502:physiology; D002453:Cell Cycle / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D027261:Fusion Regulatory Protein-1; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D027261:Fusion Regulatory Protein-1; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; D009240:N-Formylmethionine Leucyl-Phenylalanine