DIFFERENTIAL-EFFECTS OF CD4(-CELL DEPLETION ON INFLAMMATORY CENTRAL-NERVOUS-SYSTEM DISEASE, ARTHRITIS AND SIALADENITIS IN MRL() T)LPR MICE/

Autoimmune MRL/lpr mice were treated for 12-14 weeks with anti-CD4 mon oclonal antibody to define the role of CD4(+) T cells in the pathogene sis of the inflammatory central nervous system (CNS) lesions, arthriti s and sialadenitis characteristic of the strain. Anti-CD4 therapy effe ctively prevented the development of CNS lesions and arthropathic chan ges. Marked depletion of CD4(+) T cells was documented in the mononucl ear cells infiltrating the major salivary glands but the severity of s ialadenitis was significantly increased by chronic anti-CD4 immunother apy. This dissociation between beneficial and harmful effects of anti- CD4 treatment in the MRL/lpr mouse suggests that the net regulatory ef fect of CD4(+) T cells on the underlying autoimmune-mediated inflammat ory process may be positive or negative depending on the organ system involved. The pathogenetic mechanisms of inflammation and tissue destr uction in this model of systemic autoimmune disease are in some instan ces target organ-specific.