Effects of cyclosporin A on humoral immune response and resistance against vesicular stomatitis virus in mice.
The effect of cyclosporin A (CS-A) on the antiviral humoral response was studied by using vesicular stomatitis virus (VSV); VSV provided the opportunity to simultaneously assess both T-independent and T-dependent antibody responses. The T-independent anti-VSV immunoglobulin M (IgM) response was virtually unaffected, whereas the T-dependent primary anti-VSV IgG response was suppressed by CS-A; in contrast, the secondary IgG response was highly resistant to CS-A. Moreover, once the switch from IgM to IgG had occurred, the primary response also became refractory to suppression by CS-A. We concluded that the effect of CS-A on the primary anti-VSV antibody response was mediated via impairment of a T-dependent mechanism; in contrast, memory T cells or memory B cells or both were quite resistant to the suppressive effects of CS-A. CS-A treatment rendered mice highly susceptible to VSV infection; under CS-A treatment, mortality was 100% after infection via footpads, whereas immunocompetent mice survived. Since CS-A does not impair induction of early T-independent anti-VSV IgM neutralizing antibodies, this high mortality in CS-A treated mice illustrates the crucial role of CS-A-sensitive cells in resistance against VSV.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis*; D000917:Antibody Formation / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology* / Q000472:pathogenicity; D014777:Virus Diseases / Q000276:immunology
D000914:Antibodies, Viral; D003524:Cyclosporins; D007074:Immunoglobulin G; D007075:Immunoglobulin M