Suppression of virus-specific antibody production by CD8+ class I- restricted antiviral cytotoxic T cells in vivo

Dimitrios Moskofidis, H. Pircher, I. Ciernik, B. Odermatt, H. Hengartner, R. M. Zinkernagel

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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 (106 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 (102 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.

Original languageEnglish (US)
Pages (from-to)3661-3668
Number of pages8
JournalJournal of Virology
Volume66
Issue number6
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Lymphocytic choriomeningitis virus
antibody formation
Antibody Formation
Antiviral Agents
T-lymphocytes
Viruses
T-Lymphocytes
viruses
genetically modified organisms
antibodies
B-lymphocytes
cytotoxic T-lymphocytes
Cytotoxic T-Lymphocytes
B-Lymphocytes
T-Cell Antigen Receptor
Transgenic Mice
mice
receptors
spleen
Spleen

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Moskofidis, D., Pircher, H., Ciernik, I., Odermatt, B., Hengartner, H., & Zinkernagel, R. M. (1992). Suppression of virus-specific antibody production by CD8+ class I- restricted antiviral cytotoxic T cells in vivo. Journal of Virology, 66(6), 3661-3668.

Suppression of virus-specific antibody production by CD8+ class I- restricted antiviral cytotoxic T cells in vivo. / Moskofidis, Dimitrios; Pircher, H.; Ciernik, I.; Odermatt, B.; Hengartner, H.; Zinkernagel, R. M.

In: Journal of Virology, Vol. 66, No. 6, 01.01.1992, p. 3661-3668.

Research output: Contribution to journalArticle

Moskofidis, D, Pircher, H, Ciernik, I, Odermatt, B, Hengartner, H & Zinkernagel, RM 1992, 'Suppression of virus-specific antibody production by CD8+ class I- restricted antiviral cytotoxic T cells in vivo', Journal of Virology, vol. 66, no. 6, pp. 3661-3668.
Moskofidis D, Pircher H, Ciernik I, Odermatt B, Hengartner H, Zinkernagel RM. Suppression of virus-specific antibody production by CD8+ class I- restricted antiviral cytotoxic T cells in vivo. Journal of Virology. 1992 Jan 1;66(6):3661-3668.
Moskofidis, Dimitrios ; Pircher, H. ; Ciernik, I. ; Odermatt, B. ; Hengartner, H. ; Zinkernagel, R. M. / Suppression of virus-specific antibody production by CD8+ class I- restricted antiviral cytotoxic T cells in vivo. In: Journal of Virology. 1992 ; Vol. 66, No. 6. pp. 3661-3668.
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