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Virus-induced polyclonal cytotoxic T lymphocyte stimulation.

H Y Yang1, P L Dundon, S R Nahill

  • 1Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.

Journal of Immunology (Baltimore, Md. : 1950)
|March 1, 1989
PubMed
Summary

Viral infections can trigger the generation of virus-specific and allospecific cytotoxic T lymphocytes (CTL) in mice. These allospecific CTL target cells expressing foreign major histocompatibility complex (MHC) class I antigens, suggesting a broad immune response.

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Area of Science:

  • Immunology
  • Virology
  • Cellular Biology

Background:

  • Viral infections in C57BL/6 mice induce both virus-specific and allospecific cytotoxic T lymphocytes (CTL).
  • Allospecific CTL generated during viral infections exhibit reactivity against cells expressing foreign MHC class I antigens.
  • The generation of these allospecific CTL appears to be regulated by the mouse's MHC locus.

Purpose of the Study:

  • To investigate the nature and regulation of virus-induced allospecific CTL.
  • To determine the target antigens recognized by these allospecific CTL.
  • To explore the role of MHC in the generation of allospecific CTL responses.

Main Methods:

  • Infection of C57BL/6 and congenic mouse strains with various viruses (LCMV, MCMV, Pichinde, Vaccinia).

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  • Assays to measure CTL activity against allogeneic target cells.
  • Characterization of target antigens using MHC congenic strains, antibody blocking, and IFN-beta treatment.
  • Analysis of memory CTL reactivation and dependence on T helper cell factors.

    • Main Results:

    • Allospecific CTL recognized target cells expressing foreign MHC class I antigens.
    • MHC class I antigens were confirmed as targets through congenic strain analysis, antibody blocking, and IFN-beta treatment.
    • The capacity to generate high levels of allospecific CTL was MHC-regulated, with H-2b mice producing more than H-2k mice.
    • Virus infection could reactivate memory CTL, and their generation was dependent on supernatant factors from L3T4+ T cells.

    Conclusions:

    • Viral infections can induce a polyclonal CTL stimulation, generating both virus-specific and allospecific CTL.
    • MHC class I antigens are the primary targets for virus-induced allospecific CTL.
    • Lymphokines produced during viral infections may promote the proliferation and activation of non-specific CTL, broadening the immune response.