EFFECT OF IMMUNOSUPPRESSION ON CHRONIC LCM VIRUS INFECTION OF MICE

C3H mice chronically infected with LCM virus were found to be lethally affected by small doses of immunosuppression which caused bone marrow aplasia but had no effect on the amount of virus carried by the mouse. Humoral immune response of SWR/J mice to acute LCM infection was found to be totally suppressed by repeated single doses of 300 R/wk with no alteration in the level of virus carried by the mouse. In contrast, the established anti-LCM humoral immune response encountered in mice chronically infected with LCM virus was not suppressed by the same irradiation procedure. Over half of the chronic LCM carrier SWR/J mice treated with cyclophosphamide for 6 mo had total anti-LCM humoral immunosuppression, but showed no change in the level of virus carried. The glomerulonephritis which occurs in chronic LCM carrier mice was prevented by cyclophosphamide treatment in 90% of the mice. The humoral immune response which occurs in chronic LCM carrier mice appears to play no role in controlling the amount of virus carried by the mouse. Suppression of the LCM immune response by cyclophosphamide does prevent the development of glomerulonephritis in these mice

PATHOGENESIS OF THE GLOMERULONEPHRITIS OF NZB/W MICE

The development of glomerulonephritis in NZB/W mice is closely related to the formation of antinuclear, particularly anti-DNA, antibodies. The developing inflammatory glomerular lesions are characterized by the deposition of γG- and β1C-globulins plus DNA and possibly other nuclear antigens, presumably as complexes, in a granular to lumpy pattern along the capillary walls and in the mesangia. Elution studies revealed the γG-globulin in the glomeruli to be largely γG2A-type antibody to soluble nuclear antigens. Enhancement of the antinuclear antibody response by active immunization of young NZB/W mice with DNA-methylated BSA hastens the development and increases the severity of the glomerulonephritis. Similarly, injections of soluble DNA into NZB/W mice with circulating anti-DNA antibodies but with as yet little nephritis causes rapid progression of nephritis

PATHOGENESIS OF CHRONIC DISEASE ASSOCIATED WITH PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRAL INFECTION : II. RELATIONSHIP OF THE ANTI-LYMPHOCYTIC CHORIOMENINGITIS IMMUNE RESPONSE TO TISSUE INJURY IN CHRONIC LYMPHOCYTIC CHORIOMENINGITIS DISEASE

Tissue injury (chronic disease) associated with persistent LCM infection is apparently caused by the host immune response to the virus. Employing parabiosis or cell transfer from hyperimmune donors to isologous virus carriers, the tissue injury of chronic disease could be initiated and/or intensified. Furthermore, the transfer of anti-LCM antibody to SWR/J carrier mice results in acute necrotizing inflammatory lesions in regions of viral persistence, followed by chronic mononuclear infiltrates quite similar to those seen after the transfer of immune cells. The pathogenesis of the nonglomerular tissue injury of chronic LCM disease is apparently at least in part related to the interaction of circulating anti-LCM antibody with viral antigen at the tissue site. Trapping of circulating virus-antibody complexes in the glomerular filter is apparently the major cause of the glomerulonephritis

PATHOGENESIS OF CHRONIC DISEASE ASSOCIATED WITH PERSISTENT LYMPHOCYTIC CHORIOMENINGITIS VIRAL INFECTION : I. RELATIONSHIP OF ANTIBODY PRODUCTION TO DISEASE IN NEONATALLY INFECTED MICE

Mice infected shortly after birth with lymphocytic choriomeningitis (LCM) virus are not immunologically tolerant, although they carry the virus throughout life. These LCM carrier mice make anti-LCM antibody, which apparently complexes with viral antigen in the circulation and these complexes accumulate in the glomeruli. LCM carrier mice of different strains vary significantly as to concentration of detectable infectious virus in their tissue, amount and time of appearance of anti-LCM antibody, and development of an associated chronic disease. The chronic disease consists primarily of glomerulonephritis, focal hepatic necrosis, and disseminated lymphoid infiltrations. LCM carriers of the SWR/J strain contain high tissue concentrations of virus, considerable anti-LCM antibody detectable in the glomeruli by 3 wk to 2 months of age and develop chronic disease within the first 2–3 months of life. In contrast, C3H strain LCM carriers contain 1/1000 as much infectious virus, less detectable anti-LCM antibody, and have not, over a 24 month observation period, developed any detectable disease. B10D2 old and new carrier mice with intermediate amounts of virus develop chronic disease during the latter half of the first year of life. The pathogenesis of the glomerulonephritis of chronic LCM disease is apparently related to the formation of circulating virus-antibody complexes which are trapped in the glomerular filter. There is no evidence for direct glomerular injury by the virus nor for any autoimmune response by the host