title: CD28-mediated induction of proliferation in resting T cells in vitro and in vivo without engagement of the T cell receptor: evidence for functionally distinct forms of CD28.
abstract: JJ316 and JJ319 are rat CD28-specific monoclonal antibodies (mAb) of the gamma1 kappa isotype with identical co-stimulatory potency. At a concentration 100-1000-fold higher than that required for co-stimulation, JJ316, but not JJ319 induces massive proliferation of all T cell subsets in vitro without T cell receptor (TCR) triggering. "Direct" stimulation by JJ316 is fully blocked by JJ319, indicating that it is not due to cross-reactivity of JJ316 with the TCR complex or other activating receptors. JJ316 binds much more slowly to primary T cells than JJ319, whereas both antibodies bind with similar kinetics to CD28-transfected L-929 cells, suggesting that JJ316 binding to T cells requires redistribution or a conformational change of CD28. In vivo, JJ316 but not JJ319 induces rapid and transient proliferation of most CD4 T cells and, indirectly, of B cells. These data show that TCR engagement is not an absolute prerequisite either in vitro or in vivo for the induction of T cell proliferation through CD28 and suggest that mAb JJ316 is able to stimulate resting T cells directly by recruiting CD28 molecules from an inactive to an active form.
authors.affiliation: Institute for Virology and Immunobiology, University of Würzburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Tacke
authors.forename: G
authors.initials: G
authors.lastname: Hanke
authors.forename: T
authors.initials: T
authors.lastname: Hanke
authors.forename: T
authors.initials: T
authors.lastname: Hünig
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology*; D002455:Cell Division; D005260:Female; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497966:Cd86 protein, rat; C568777:JJ 316; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell