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Qualitative and quantitative requirements for CD4(+) T cell-mediated antiviral protection

Academic Article
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Overview

authors

  • Maloy, K. J.
  • Burkhart, C.
  • Freer, G.
  • Rulicke, T.
  • Pircher, H.
  • Kono, Dwight
  • Theofilopoulos, Argyrios
  • Ludewig, B.
  • Hoffmann-Rohrer, U.
  • Zinkernagel, R. M.
  • Hengartner, H.

publication date

  • March 1999

journal

  • Journal of Immunology  Journal

abstract

  • CD4+ Th cells deliver the cognate and cytokine signals that promote the production of protective virus-neutralizing IgG by specific B cells and are also able to mediate direct antiviral effector functions. To quantitatively and qualitatively analyze the antiviral functions of CD4+ Th cells, we generated transgenic mice (tg7) expressing an MHC class II (I-Ab)-restricted TCR specific for a peptide derived from the glycoprotein (G) of vesicular stomatitis virus (VSV). The elevated precursor frequency of naive VSV-specific Th cells in tg7 mice led to a markedly accelerated and enhanced class switching to virus-neutralizing IgG after immunization with inactivated VSV. Furthermore, in contrast to nontransgenic controls, tg7 mice rapidly cleared a recombinant vaccinia virus expressing the VSV-G (Vacc-IND-G) from peripheral organs. By adoptive transfer of naive tg7 CD4+ T cells into T cell-deficient recipients, we found that 105 transferred CD4+ T cells were sufficient to induce isotype switching after challenge with a suboptimal dose of inactivated VSV. In contrast, naive transgenic CD4+ T cells were unable to adoptively confer protection against peripheral infection with Vacc-IND-G. However, tg7 CD4+ T cells that had been primed in vitro with VSV-G peptide were able to adoptively transfer protection against Vacc-IND-G. These results demonstrate that the antiviral properties of CD4+ T cells are governed by the differentiation status of the CD4+ T cell and by the type of effector response required for virus elimination.

subject areas

  • Adoptive Transfer
  • Animals
  • Antibodies, Viral
  • CD4-Positive T-Lymphocytes
  • Female
  • Immunoglobulin Class Switching
  • Immunoglobulin G
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell, alpha-beta
  • Vesicular stomatitis Indiana virus
  • Viral Envelope Proteins
  • Virus Diseases
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 10072535
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Additional Document Info

start page

  • 2867

end page

  • 2874

volume

  • 162

issue

  • 5

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