TREATMENT WITH ANTIGRANULOCYTE ANTIBODIES INHIBITS THE EFFECTOR PHASEOF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Emerging data suggest that polymorphonuclear leukocytes (PMNLs) can pl ay an important role in Ag-dependent immune responses. Therefore, we h ave assessed the involvement of these cells in the development of an o rgan-specific autoimmune disease, experimental autoimmune encephalomye litis (EAE), in the mouse, Depletion of peripheral blood PMNLs beginni ng day 8 after immunization significantly delayed and in some cases to tally prevented the development of clinical EAE in mice. Depletion of PMNLs beginning 1 day before sensitization and continuing until day 7 postimmunization had no effect on the subsequent development of EAE, s uggesting that depletion alters the efferent but not the afferent arm of the immune response. In vitro studies showed that lymphoid cells fr om mice protected from EAE by PMNL depletion beginning on day 8 postse nsitization proliferated in response to specific Ag to a level equal t o cells from sensitized animals treated with control serum, again indi cating that treatment was not affecting the afferent limb of the immun e response. Further evidence that PMNL may be necessary in initiating the pathology of EAE was seen in passive transfer experiments where PM NL-depleted recipients of MBP-specific lymphoid effector cells develop ed EAE much less effectively than did animals treated with control Ab, Taken together, these data indicate that PMNLs play a critical role i n the effector phase of the development of the clinicopathologic expre ssion of EAE in mice.