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Media type:
E-Article
Title:
CD8 T Cells Inhibit IgE Via Dendritic Cell IL-12 Induction That Promotes Th1 T Cell Counter-Regulation
Contributor:
Thomas, Matthew J.;
Noble, Alistair;
Sawicka, Ela;
Askenase, Philip W.;
Kemeny, David M.
imprint:
The American Association of Immunologists, 2002
Published in:The Journal of Immunology
Language:
English
DOI:
10.4049/jimmunol.168.1.216
ISSN:
1550-6606;
0022-1767
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title>
<jats:p>Th1 and Th2 cells are counterinhibitory; their balance determines allergic sensitization. We show here that CD8 T cell subsets break these rules as both T cytotoxic (Tc)1 and Tc2 cells promote Th1 over Th2 immunity. Using IL-12−/−, IFN-γ−/−, and OVA257–264-specific Vα2Vβ5 TCR-transgenic mice, we have identified the key steps involved. OVA-specific IFN-γ−/− CD8 T cells inhibited IgE responses equivalent to wild-type CD8 T cells (up to 98% suppression), indicating that CD8 T cell-derived IFN-γ was not required. However, OVA-specific CD8 T cells could not inhibit IgE in IFN-γ−/− recipients unless reconstituted with naive, wild-type CD4 T cells, suggesting that CD4 T cell-derived IFN-γ did play a role. Transfer of either Tc1 or Tc2 Vα2Vβ5 TCR-transgenic CD8 T cells inhibited IgE and OVA-specific Th2 cells while promoting OVA-specific Th1 cell responses, suggesting a potential role for a type 1 inducing cytokine such as IL-12. CD8 T cells were shown to induce IL-12 in OVA257–264-pulsed dendritic cells (DC) in vitro. Furthermore, CD8 T cells were unable to inhibit IgE responses in IL-12−/− recipients without the addition of naive, wild-type DC, thus demonstrating a pivotal role for IL-12 in this mechanism. These data reveal a mechanism of IgE regulation in which CD8 T cells induce DC IL-12 by an IFN-γ-independent process that subsequently induces Th1 and inhibits Th2 cells. Th1 cell IFN-γ is the final step that inhibits B cell IgE class switching. This demonstrates a novel regulatory network through which CD8 T cells inhibit allergic sensitization.</jats:p>