title: Suppression of virus-specific antibody production by CD8+ class I-restricted antiviral cytotoxic T cells in vivo.
abstract: The question of whether virus-induced immunosuppression includes the antibody response against the infecting virus itself was evaluated in a model situation. Transgenic mice expressing the T-cell receptor (TCR) specific for peptide 32-42 of lymphocytic choriomeningitis virus (LCMV) glycoprotein 1 presented by Db reacted with a strong transgenic cytotoxic T-lymphocyte (CTL) response starting on day 3 after infection with a high dose (10(6) PFU intravenously [i.v.]) of the WE strain of LCMV (LCMV-WE); LCMV-specific antibody production in the spleen was suppressed in these mice. Low-dose (10(2) PFU i.v.) infection resulted in an antiviral antibody response comparable to that of the transgene-negative littermates. The induction of suppression of LCMV-specific antibody responses was specifically mediated by CD8+ TCR transgenic CTLs, since the LCMV-8.7 variant virus (which is not recognized by transgenic TCR-expressing CTLs because of a point mutation) did not induce suppression. In addition, treatment with CD8 monoclonal antibody in vivo abrogated suppression. Once suppression had been established, it was found to be nonspecific. The abrogation of antibody responses depended on the relative kinetics of the antibody response involved and the kinetics of the anti-LCMV CTL response. Analysis of T- and B-cell subpopulations showed no significant changes, but immunohistochemical analysis of spleens revealed extensive destruction of follicular organization in lymphoid tissue by day 4 in transgenic mice infected with LCMV-WE but not in those infected with the CTL escape mutant LCMV-8.7. Impairment of antigen presentation rather than of T or B cells was also suggested by adoptive transfer experiments, showing that transferred infected macrophages may improve the anti-LCMV antibody response in LCMV-immunosuppressed transgenic recipients; also, T and B cells from suppressed transgenic mice did respond in irradiated and virus-infected nontransgenic mice with antibody formation to LCMV. Such virus-triggered, T-cell-mediated immunopathology causing the suppression of B cells and of protective antibody responses, including those against the infecting virus itself, may permit certain viruses to establish persistent infections.
authors.affiliation: Department of Pathology, University of Zürich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Moskophidis
authors.forename: H
authors.initials: H
authors.lastname: Pircher
authors.forename: I
authors.initials: I
authors.lastname: Ciernik
authors.forename: B
authors.initials: B
authors.lastname: Odermatt
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000914:Antibodies, Viral / Q000096:biosynthesis*; D016827:CD8 Antigens / Q000276:immunology*; D005805:Genes, MHC Class I; D007075:Immunoglobulin M / Q000302:isolation & purification; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D012680:Sensitivity and Specificity; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016378:Tissue Transplantation; D014759:Viral Envelope Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016827:CD8 Antigens; D007075:Immunoglobulin M; D010446:Peptide Fragments; D014759:Viral Envelope Proteins