Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody.
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.
Hughes
C
C
Division of Rheumatology, Children's Hospital Medical Center, University of Cincinnati, OH 45229.
Wolos
J A
JA
Giannini
E H
EH
Hirsch
R
R
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*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D003094:Collagen