SHORT-TERM TREATMENT WITH SOLUBLE NEUROANTIGEN AND ANTI-CD11A (LFA-1)PROTECTS RATS AGAINST AUTOIMMUNE ENCEPHALOMYELITIS - TREATMENT ABROGATES AUTOIMMUNE-DISEASE BUT NOT AUTOIMMUNITY

Resistance to autoimmune encephalomyelitis was induced by s.c. infusio n of myelin basic protein (MBP) in saline in combination with i.p. inj ections of anti-CD11a (LFA-1) mAbs. This treatment induces resistance to EAE induction, which appears early and persists for at least one mo nth after treatment. Some MBP-CFA-challenged resistant rats showed min imal inflammation in the central nervous system, which was, however, c onfined to the meninges of the lower spinal cord. Examination of the i mmune status of MBP-anti-LFA-1 treated rats before encephalitogenic ch allenge failed to reveal any priming when assessed by Ag driven prolif eration and cytokine production by lymphoid cells, and by circulating Ab production. Following challenge of protected rats, lymph node cell proliferation to MBP was unaltered, indicating that reactive cells had not been deleted or anergized. Resistance could not be transferred wi th lymphoid cells from treated rats nor abrogated by cyclophosphamide treatment. In treated rats following challenge, there was a shift in t he isotype of anti-MBP Ab produced, from an IgG2a:IgG1 ratio of 2:1 to 1:1, due to an increase in IgG1 production, indicating a possible bia s towards a nonpathogenic Th2 CD4(+) T cell response. The IgG1 Ab was detected early after challenge suggesting that pretreatment had indeed primed the animals, and had primed them to go down the Th2 pathway fo llowing encephalitogenic challenge. The ability to divert immune react ivity from a destructive to a nondestructive response could have impor tant therapeutic implications for autoimmune disease.