Inhibition of diabetes in BB rats by virus infection. II. Effect of virus infection on the immune response to non-viral and viral antigens.
Lymphocytic choriomeningitis virus (LCMV) infection prevents the usual insulin-dependent diabetes mellitus of aged BB rats (Dyrberg, Schwimmbeck & Oldstone, 1988; Schwimmbeck, Dyrberg & Oldstone, 1988). In this study earlier observations are extended by noting that LCMV infection substantially alters the immune responsesof BB diabetic-prone (dp) rats. The control, uninfected rats make vigorous primary and secondary antibody responses when challenged with keyhole limpet haemocyanin (KLH), human immunoglobulin (HuIg) or sheep red blood cells (SRBC). Such rats fail to mount a primary response to bovine serum albumin (BSA) but do produce a moderate secondary response. They mount good antibody responses to LCMV but fail to generate either primary or secondary LCMV-specific cytotoxic T-lymphocyte (CTL) responses or CTL responses to Pichinde virus. In contrast, BB dp rats acutely infected with LCMV generate no primary immune responses to SRBC, KLH or BSA and only meager responses when challenged with HuIg. They mount secondary responses to KLH, HuIg and BSA that approximate those of their uninfected litter mates, but have a comparatively lower response to SRBC. LCMV binds to and infects lymphocytes of the BB dp rat. Binding is enhanced over that observed with lymphocytes from BB diabetic-resistant (dr) rats, which are able to generate CTL immune responses to LCMV and Pichinde viruses. Hence, lymphocytes from BB dp rats are uniquely susceptible to binding and replication of LCMV. During the acute stage of LCMV infection, a general primary T-cell immunosuppression occurs with respect to a variety of viral and non-viral antigens. Over time, responsiveness to T-cell dependent antigens returns except for the ability to generate CTL responses to LCMV or the autoimmune response(s) required to cause insulin-dependent diabetes mellitus.
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Department of Neuropharmacology, Scripps Clinic, La Jolla, California 91037.
Tishon
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A
Oldstone
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MB
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000941:Antigens / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D007108:Immune Tolerance; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051381:Rats; D011913:Rats, Inbred BB; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000914:Antibodies, Viral; D000941:Antigens; D000956:Antigens, Viral