Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells

M. Battegay, Dimitrios Moskofidis, H. Waldner, M. A. Brundler, W. P. Fung-Leung, T. W. Mak, H. Hengartner, R. M. Zinkernagel

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Abstract

After infection with some viruses that tend to persist, neutralizing antibodies are generated rather late, i.e., after 1 to 3 mo. This has been observed for HIV, Hepatitis B infection in man, or after infection with lymphocytic choriomeningitis virus (LCMV) in mice. In contrast, nonneutralizing antibodies to LCMV are generated by day 7 and reach high titers by day 10. This study attempts to evaluate reasons for late and low titered neutralizing antibody responses. After a primary infection with low doses (102 plaque forming units) of the poorly cytopathic LCMV-WE, neutralizing antibodies were rarely produced at detectable levels before days 60 to 120. In vivo depletion of CD8+ CTL led to a marked enhancement and acceleration of kinetics of the neutralizing antibody response. In contrast, nonneutralizing antibodies, including those specific for LCMV-GP carrying the neutralizing determinant, were detectable very early, i.e., 4 to 7 days after infection, with maximum titers usually by day 10 irrespective of the presence or absence of CTL. Mice completely lacking CD8+ T cells because of deletion by homologous recombination (CD8(-/-)) also exhibited neutralizing antibodies early by day 10 to 20, and by day 120 reached very high titers. The neurotropic isolate LCMV-ARMSTRONG induced low but significant titers of neutralizing antibodies relatively early (i.e., by days 7 to 10), whereas the lympho-viscerotrope mutant virus LCMV-ARMSTRONG Cl-13 did not. Early and effective CTL responses causing immunopathology (and immunosuppression) correlated with the absence of neutralizing antibodies. The discrepancy between the CTL-dependent inhibition of neutralizing versus unimpaired anti- GP ELISA responses cannot be explained by different Ag doses alone. Additionally, it may reflect different kinetics of the responses, whereby the later neutralizing responses possibly requiring IgG affinity maturation may be more susceptible to general immunosuppression; also B cells expressing neutralizing receptors, but not those with antibodies binding GP (or NP), may be actively infected, therefore they present viral peptides on class I MHC Ag and may become targets for anti-LCMV-specific CTL.

Original languageEnglish (US)
Pages (from-to)5408-5415
Number of pages8
JournalJournal of Immunology
Volume151
Issue number10
StatePublished - Jan 1 1993
Externally publishedYes

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Lymphocytic choriomeningitis virus
Neutralizing Antibodies
Antibody Formation
Antiviral Agents
Viruses
T-Lymphocytes
Infection
Immunosuppression
Antibodies
Homologous Recombination
Hepatitis B
B-Lymphocytes
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
HIV
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Battegay, M., Moskofidis, D., Waldner, H., Brundler, M. A., Fung-Leung, W. P., Mak, T. W., ... Zinkernagel, R. M. (1993). Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. Journal of Immunology, 151(10), 5408-5415.

Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. / Battegay, M.; Moskofidis, Dimitrios; Waldner, H.; Brundler, M. A.; Fung-Leung, W. P.; Mak, T. W.; Hengartner, H.; Zinkernagel, R. M.

In: Journal of Immunology, Vol. 151, No. 10, 01.01.1993, p. 5408-5415.

Research output: Contribution to journalArticle

Battegay, M, Moskofidis, D, Waldner, H, Brundler, MA, Fung-Leung, WP, Mak, TW, Hengartner, H & Zinkernagel, RM 1993, 'Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells', Journal of Immunology, vol. 151, no. 10, pp. 5408-5415.
Battegay M, Moskofidis D, Waldner H, Brundler MA, Fung-Leung WP, Mak TW et al. Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. Journal of Immunology. 1993 Jan 1;151(10):5408-5415.
Battegay, M. ; Moskofidis, Dimitrios ; Waldner, H. ; Brundler, M. A. ; Fung-Leung, W. P. ; Mak, T. W. ; Hengartner, H. ; Zinkernagel, R. M. / Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. In: Journal of Immunology. 1993 ; Vol. 151, No. 10. pp. 5408-5415.
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