title: Differential response of CD4+ V7+ and CD4+ V7- T cells to T cell receptor-dependent signals: CD4+ V7+ T cells are co-stimulation independent and anti-V7 antibody blocks the induction of anergy by bacterial superantigen.
abstract: V7 is a novel cell surface glycoprotein that is expressed on 25% of circulating T lymphocytes. This molecule appears to play a critical role in T cell activation based on the observation that a monoclonal anti-V7 antibody inhibits T cell receptor (TCR)-dependent interleukin-2 (IL-2) production and proliferation of T cells. In the current study, CD4+ V7+ and CD4+ V7- T cells were separated from one another and their response to various stimuli analyzed. Although there were only minor differences between the two subsets in the expression of activation/differentiation markers, including CD45RA and R0 isotypes, when exposed to immobilized anti-CD3 or anti-TCR antibodies in the absence of APC, CD4+ V7+ T cells alone produced IL-2 and proliferated vigorously. By contrast, CD4+ V7- cells responded poorly to such stimuli, but they recovered their capacity to respond if antigen-presenting cells (APC) or anti-CD28-antibody were added to the cultures. The enhancement of the V7- T cell response by APC appears to be related to augmentation of TCR signals because the effect could be blocked by antibodies against molecules on APC [major histocompatibility (MHC) class II, CD86] that are known to up-regulate such signals through their interaction with counter-receptors on T cells. To assess the role of V7 in a system independent of co-stimulation, CD4+ T cells were stimulated with the bacterial superantigens, staphylococcal enterotoxins A and B. The cells responded by proliferating and then becoming anergic. Addition of anti-V7 antibody at the initiation of culture with superantigen did not inhibit cellular proliferation but prevented T cells from becoming anergic, while addition of anti-CD28 antibody had no effect on either proliferation or anergy induction. These results indicate that V7 and CD28 mediate distinct intracellular signals and suggest that V7 functions to preserve T cell reactivity whether the stimulus is mitogenic or anergizing.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Soares
authors.forename: A
authors.initials: A
authors.lastname: Rivas
authors.forename: C
authors.initials: C
authors.lastname: Ruegg
authors.forename: E G
authors.initials: EG
authors.lastname: Engleman
mesh_terms: D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial / Q000494:pharmacology*; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology; D001427:Bacterial Toxins; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology*
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001427:Bacterial Toxins; C093213:CD101 antigen, human; D017252:CD3 Complex; D004768:Enterotoxins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C026066:enterotoxin A, Staphylococcal