Delayed-type hypersensitivity response in experimental autoimmune neuritis treated with peptide-coupled spleen cells.
Experimental autoimmune neuritis (EAN) is a T cell-mediated autoimmune inflammatory disease of the peripheral nervous system that is characterized by demyelination and mononuclear cell infiltration. It is induced in Lewis rats by administration of myelin P2 protein or a synthetic peptide (SP-26) corresponding to amino acid residues 53-78 of bovine P2 protein. Recently, we showed that SP-26, when coupled to syngeneic spleen cells and administered intravenously, provided an effective means of inducing tolerance by inhibiting the clinical signs, decreased proliferative response of lymphoid cells to SP-26 and histological changes of EAN. However, our current data indicate that, despite tolerance induction in these Lewis rats, the antigen-specific delayed-type hypersensitivity (DTH) response to SP-26 remained intact. Furthermore, interferon (IFN)-gamma production by spleen cells of tolerized rats were unchanged as compared to EAN rats. The in vitro proliferation of T lymphocytes from tolerized rats stimulated by SP-26 was reduced as compared to EAN controls but was enhanced upon addition of exogenous interleukin-2. Thus, reduction in EAN clinical signs does not necessarily indicate a decrease in DTH response and IFN-gamma production in EAN Lewis rats. The implication of this finding in regard to immunoregulatory mechanism of DTH response is discussed.
Gregorian
S K
SK
Department of Immunology, Genentech, South San Francisco, CA 94080.
Rostami
A
A
D000818:Animals; D017690:Cell Transplantation; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000378:metabolism*; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000628:therapy*; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma