NK cells help to induce CD8+-T-cell immunity against Toxoplasma gondii in the absence of CD4+ T Cells

Crescent L. Combe, Tyler J. Curiel, Magali M. Moretto, Imtiaz A. Khan

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

CD8+ T-cell immunity plays an important role in protection against intracellular infections. Earlier studies have shown that CD4 + T-cell help was needed for launching in vivo CD8+ T-cell activity against these pathogens and tumors. However, recently CD4+ T-cell-independent CDS responses during several microbial infections including those with Toxoplasma gondii have been described, although the mechanism is not understood. We now demonstrate that, in the absence of CD4+ T cells, T. gondii-infected mice exhibit an extended NK cell response, which is mediated by continued interleukin-12 (IL-12) secretion. This prolonged NK cell response is critical for priming parasite-specific CD8+ T-cell immunity. Depletion of NK cells inhibited the generation of CD8+ T-cell immunity in CD4-/- mice. Similarly neutralization of IL-12 reduces NK cell numbers in infected animals and leads to the down-regulation of CD8 + T-cell immunity against T. gondii. Adoptive transfer of NK cells into the IL-12-depleted animals restored their CD8+ T-cell immune response, and animals exhibited reduced mortality. NK cell gamma Interferon was essential for cytotoxic T-lymphocyte priming. Our studies for the first time demonstrate that, in the absence of CD4+ T cells, NK cells can play an important role in induction of primary CD8+ T-cell immunity against an intracellular infection. These observations have therapeutic implications for immunocompromised individuals, including those with human immunodeficiency virus infection.

Original languageEnglish (US)
Pages (from-to)4913-4921
Number of pages9
JournalInfection and immunity
Volume73
Issue number8
DOIs
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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