title: Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody.
abstract: Autoimmune diseases can be characterized by increases in Th cell activities, suggesting that inhibition of Th cell function might ameliorate autoimmunity. We have recently reported that administration of nonmitogenic anti-CD3 mAb (nmCD3) to nonautoimmune mice can induce long-term Th cell hyporesponsiveness, reflected by reduced IL-2 secretion upon re-exposure to Ag. This study was designed to determine the effects of nmCD3 on autoimmunity by using the murine collagen-induced arthritis model. Treatment of DBA/1 mice with nmCD3 delayed the onset and reduced the severity of arthritis in mice immunized with type II collagen (CII). This effect was not caused by depletion of T cells or modulation of TCR. The observed inhibition of arthritis was not caused by decreased Ab production, as anti-CII titers were not affected. Rather, lymph node cells from CII-immunized mice treated with nmCD3 were hyporesponsive to in vitro stimulation with CII. This hyporesponsiveness was reflected by a marked decrease in secretion of IL-2 and IFN-gamma, but not of IL-4, which suggests that nmCD3 had its principal effect on Th1 cells. The hyporesponsiveness was not Ag-specific, because IL-2 and IFN-gamma production in response to a pan-T cell mitogen was also reduced. These results demonstrate that induction of Th1 cell hyporesponsiveness with nmCD3 can significantly alter the course of CIA and suggest that IL-2 and/or IFN-gamma play a crucial role in disease pathogenesis.
authors.affiliation: Division of Rheumatology, Children's Hospital Medical Center, University of Cincinnati, OH 45229.
authors.forename: C
authors.initials: C
authors.lastname: Hughes
authors.forename: J A
authors.initials: JA
authors.lastname: Wolos
authors.forename: E H
authors.initials: EH
authors.lastname: Giannini
authors.forename: R
authors.initials: R
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D001168:Arthritis / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D003094:Collagen / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D003094:Collagen