Monocyte-independent T-cell activation by polyclonal antithymocyte globulins.
The in vitro mitogenic properties of polyclonal antithymocyte and antilymphocyte globulins (ATG) on peripheral blood mononuclear cells were investigated. The ATG were mitogenic in a dose-dependent manner with maximal proliferation observed at 250 or 500 micrograms/ml. ATG activated blastogenesis of CD4+, CD8+, and CD57+ (NK cells) lymphocytes. The ATG induced interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) gene expression and lymphokine secretion in cell culture supernatant and IL-2 receptor (CD25) expression. At submitogenic concentrations ATG potentialized the effect of phorbol esters on T cell proliferation, but not that of calcium ionophore. The mitogenic effect of ATG was not abrogated by monocyte depletion indicating that like CD2 monoclonal antibodies (mAbs) ATG activate T cells via a monocyte-independent pathway. CD3 and CD2 mAbs which activate T cells without binding to B surface determinants stimulated the proliferation of B cells and their differentiation into immunoglobulin (Ig)-secreting cells. In contrast, ATG induced only a transient B cell activation, but failed to support B cell differentiation into Ig-secreting cells despite the secretion of IL-2. These properties shared by ATG obtained in horses or rabbits by immunization with different cell types appear to differ from those of other T cell mitogens.
Bonnefoy-Berard
N
N
Laboratory of Immunology, INSERM U80 CNRS URA1177 UCBL, Hôpital E. Herriot, Lyon, France.
Vincent
C
C
Verrier
B
B
Revillard
J P
JP
D000917:Antibody Formation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D000961:Antilymphocyte Serum / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D016131:Lymphocyte Subsets / Q000276:immunology; D008222:Lymphokines / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015703:Antigens, CD; D000961:Antilymphocyte Serum; D007376:Interleukin-2; D008222:Lymphokines; D008934:Mitogens; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate