title: Human gamma delta T cells are resistant to induction of anergy but not to induction of cell death in vitro.
abstract: A condition of hyporesponsiveness can be induced in certain mature human alpha beta (TCR2) cells relatively easily by their stimulation in the absence of costimulatory signals (signal 1 alone). This state of "anergy" has been implicated in tolerance to self and transplanted organs as well as tumors and may represent an important regulatory component of immune responsiveness. Little is known about whether the same condition applies to gamma delta (TCR1) cells. We therefore undertook to investigate anergy induction in TCR1 cell clones using several approaches known to induce this state in TCR2 cells. First, TCR1 clones were found not to be anergized by culture on immobilized CD3 monoclonal antibody (mAb), while the majority of TCR2 clones were anergized. Second, blocking of autocrine proliferation (stimulated in TCR1 or TCR2 clones by mitogen in the presence of accessory cells) using CTLA-4-lg, a soluble B7 family counterreceptor resulted in anergy induction in TCR2 cells but not TCR1 cells, although experiments with CHO cells transfected with B7-1 (CD80) genes confirmed that these TCR1 clones were responsive to costimulation with B7. Third, blocking mitogen-induced proliferation with anti-IL 2 receptor antibodies and anti-IL 2 antisera resulted in anergy induction in TCR2 but not TCR1 cells. Fourth, stimulation with the calcium ionophore ionomycin also anergized TCR2 but not TCR1 cells. In all four systems, but especially in the latter, stimulation by signal 1 alone resulted in high levels of cell death (> 50%) which was similar for both TCR1 and TCR2 cells. Therefore, these data may reflect a high level of resistance to tolerance induction (manifested as proliferative anergy) but not to clonal deletion (manifested as stimulation-dependent cell death) on the part of TCR1 cells.
authors.affiliation: Second Department of Internal Medicine, University Hospital, Tübingen, Federal Republic of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Pawelec
authors.forename: H
authors.initials: H
authors.lastname: Friccius
authors.forename: M
authors.initials: M
authors.lastname: Boshell
authors.forename: P
authors.initials: P
authors.lastname: Siegels-Hübenthal
authors.forename: A
authors.initials: A
authors.lastname: Rehbein
authors.forename: E
authors.initials: E
authors.lastname: Schlotz
authors.forename: H
authors.initials: H
authors.lastname: Pohla
authors.forename: K
authors.initials: K
authors.lastname: Schaudt
authors.forename: D
authors.initials: D
authors.lastname: Sansom
mesh_terms: D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D060908:CTLA-4 Antigen; D016923:Cell Death / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D018796:Immunoconjugates; D016130:Immunophenotyping / Q000379:methods; D007376:Interleukin-2 / Q000276:immunology; D015759:Ionomycin / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D007376:Interleukin-2; D008934:Mitogens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D000069594:Abatacept