Rafi Ahmed1,2,3,4,5, A. Salmi1,2,3,4,5, L D Butler1,2,3,4,5, Jacques M. Chiller1,2,3,4,5, M B Oldstone1,2,3,4,5
1From the Department of lmmunology, Scripps Clinic and Research Foundation, La Jolla, California 92037
2Lilly Research Laboratories, Indianapolis, IN 46285; J. Chiller,
3Lilly Research Laboratories, San Diego, CA.
4Sam Dales, University of Western Ontario, London, Ontario, Canada.
5ment of Virology, University of Turku, Finland; L. Butler,
Tóm tắt
We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV -specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV -specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence.
