The NOD (nonobese diabetic) mouse has been studied as an animal model for autoimmune insulindependent diabetes and Sjögren's syndrome. NOD.Ig null mice, which lack functional B lymphocytes, develop progressive histopathologic lesions of the submandibular and lachrymal glands similar to NOD mice, but in the absence of autoimmune insulitis and diabetes. Despite the focal appearance of T cells in salivary and lachrymal tissues, NOD.Ig null mice fail to lose secretory function as determined by stimulation of the muscarinic͞cholinergic receptor by the agonist pilocarpine, suggesting a role for B cell autoantibodies in mediating exocrine dryness. Infusion of purified serum IgG or F(ab) 2 fragments from parental NOD mice or human primary Sjögren's syndrome patients, but not serum IgG from healthy controls, alters stimulated saliva production, an observation consistent with antibody binding to neural receptors. Furthermore, human patient IgG fractions competitively inhibited the binding of the muscarinic receptor agonist, [ 3 H]quinuclidinyl benzilate, to salivary gland membranes. This autoantibody activity is lost after preadsorption with intact salivary cells. These findings indicate that autoantibodies play an important part in the functional impairment of secretory processes seen in connection with the autoimmune exocrinopathy of Sjögren's syndrome.

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It has previously been reported that synthetic peptides correspondg to sequences derived from T-cell receptor variable regions identified as dominant in the T-cellmediated autoimmune disease experimental allergic encephalomyclitis in both the mouse and the rat can down-regulate disease in Lewis rats. In contrast to these results, we have found that immunization of Lewis rats with such peptides in complete Freund's adjuvant prior to induction of experimental allergic encephalomyelitis with myelin basic protein leads to responses ranging from profound disease enhancement to lack of disease. In some cases, enhanced disease was followed by a prolonged neurologic deficit that resembles multiple sclerosis more closely than does acipte experimental allergic encephalomyelitis. These findings, on the one hand, support previous results showing T-cell receptor peptide-induced modulation of the disease experimental allergic encephalomyelitis and, on the other, indicate that such immunization is not a reliable method for inducing suppression of encephalitogenic effector cells.The finding that a limited set ofT cells, in the mouse (1-3) and the rat (4, 5), mediates the autoimmune disease of the central nervous system experimental allergic encephalomyelitis (EAE) suggests the possibility of immune intervention by clonal-specific regulation. In both species, T cells bearing the T-cell receptor (TCR) variable (V) regions V(88.2 and Va2/4 are the dominant disease-causing population (6). Monoclonal antibodies directed against these TCR V regions have been shown to block the expression of EAE in response to myelin basic protein (MBP) in Lewis rats (7), and similar antibodies have both blocked disease and suppressed ongoing disease in mice (1-3). Recently, evidence of disease suppression in rats after immunization with synthetic peptides corresponding to portions of the V a and V a chains of identified autoreactive T-cell clones has been seen (8, 9). We now report that immunization of Lewis rats with peptides representing the V regions ofthese dominant TCRs can hasten disease onset and increase the severity and duration of disease.We constructed three peptides derived from both TCR chains of the T-cell hybridoma 5.10, which is specific for the encephalitogenic determinant of MBP (4): the Ja39 peptide with the sequence RFGAGTRLTVK (8), the CDR2-Vf8 peptide with the sequence DMGHGLRLIHYSYDVN-STEKG (9), and TK20 representing the N-terminal residues 5-24 of rat Vf38.2 (4) with the sequence TQSPRNKVALTG-GKVTLSCK. Rats were immunized with these peptides in complete Freund's adjuvant (CFA) prior to induction of EAE with MBP, and responses ranging from profound disease enhancement to the lack of disease were obtained. In some cases, enhancement of disease was followed by a prolonged neurologic deficit, something we have not previously observed in MBP-induced EAE, which is generally an acute self-limiting disease. This chronic condition is of considerable interest in that it more closely resembles multiple sclerosis than does the acu...

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