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PMID: 9841916 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Resting respiratory tract dendritic cells preferentially stimulate T helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction of Th1 immunity.

The Journal of experimental medicine ·Vol. 188 ·No. 11 ·1998-12-07 ·Pages 2019-31

Stumbles PA, Thomas JA, Pimm CL, Lee PT, Venaille TJ, Proksch S, Holt PG

Abstract

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.

MeSH Terms
Animals CD40 Antigens/immunology Cytokines/immunology Dendritic Cells/immunology Immunity, Cellular Immunity, Mucosal/immunology Oligonucleotides, Antisense Rats Rats, Inbred Strains Respiratory System/cytology,immunology Signal Transduction/immunology Th1 Cells/immunology Th2 Cells/immunology
Chemicals
CD40 Antigens Cytokines Oligonucleotides, Antisense
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Stumbles P A
TVW Telethon Institute for Child Health Research (affiliated with the University of Western Australia), West Perth, Western Australia 6872, Australia.
Thomas J A
Pimm C L
Lee P T
Venaille T J
Proksch S
Holt P G
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.188.11.2019
Published
1998-12-07
Pages
2019-31
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212375
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.188.11.2019 PMC Full Text View journal details
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