Differential effects of CD4+ T cell depletion on inflammatory central nervous system disease, arthritis and sialadenitis in MRL/lpr mice.

Abstract

Autoimmune MRL/lpr mice were treated for 12-14 weeks with anti-CD4 monoclonal antibody to define the role of CD4+ T cells in the pathogenesis of the inflammatory central nervous system (CNS) lesions, arthritis and sialadenitis characteristic of the strain. Anti-CD4 therapy effectively prevented the development of CNS lesions and arthropathic changes. Marked depletion of CD4+ T cells was documented in the mononuclear cells infiltrating the major salivary glands but the severity of sialadenitis was significantly increased by chronic anti-CD4 immunotherapy. This dissociation between beneficial and harmful effects of anti-CD4 treatment in the MRL/lpr mouse suggests that the net regulatory effect of CD4+ T cells on the underlying autoimmune-mediated inflammatory process may be positive or negative depending on the organ system involved. The pathogenetic mechanisms of inflammation and tissue destruction in this model of systemic autoimmune disease are in some instances target organ-specific.