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Induction of CTL and nonpolarized Th cell responses by CD8alpha(+) and CD8alpha(-) dendritic cells

G Schlecht1, C Leclerc, G Dadaglio

  • 1Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.

Journal of Immunology (Baltimore, Md. : 1950)
|October 10, 2001
PubMed

Insights

Both CD8alpha(+) and CD8alpha(-) dendritic cell (DC) subsets effectively induce cytotoxic T lymphocyte (CTL) responses. CD8alpha(-) DCs promote a stronger Th2 response, while CD4(+) T cell responses do not impact CD8(+) CTL development.

Area of Science:

  • Immunology
  • Cell Biology
  • T cell immunology

Background:

  • Two distinct mouse dendritic cell (DC) subpopulations, CD8alpha(+) and CD8alpha(-), differ in CD8alpha expression and lymphoid organ localization.
  • Evidence suggests functional differences between CD8alpha(+) and CD8alpha(-) DC subsets.

Purpose of the Study:

  • To analyze CD4(+) and CD8(+) T cell responses after intravenous injection of peptide-pulsed DC subsets.
  • To determine the functional differences between CD8alpha(+) and CD8alpha(-) DC subsets in T cell priming.

Main Methods:

  • Utilized MHC class I- and/or class II-restricted peptides for DC stimulation.
  • Administered freshly purified peptide-pulsed DC subsets intravenously (i.v.).
  • Analyzed T cell responses, including CTL induction and cytokine production (Th1, Th2).

Main Results:

  • Both DC subsets induced specific CTL responses and Th1 cytokine production without CD4(+) T cell priming.
  • In vivo CD4(+) T cell activation by either DC subset resulted in nonpolarized Th responses (Th1 and Th2 cytokines).
  • CD8alpha(-) DCs induced higher IL-4 and IL-10 (Th2 cytokines) than CD8alpha(+) DCs; IL-5 was produced by both.
  • When both CD4(+) and CD8(+) T cells were primed, Th1 cytokines were mainly from CD8(+) T cells and Th2 from CD4(+) T cells.

Conclusions:

  • CD4(+) T cell responses do not influence the development of CD8(+) T cell cytotoxic responses induced by either CD8alpha(+) or CD8alpha(-) DC subsets.
  • Both DC subsets are capable of inducing CTL responses, with distinct profiles for Th cytokine induction.

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