A new subset of CD103+CD8alpha+ dendritic cells in the small intestine expresses TLR3, TLR7, and TLR9 and induces Th1 response and CTL activity

J Immunol. 2011 Jun 1;186(11):6287-95. doi: 10.4049/jimmunol.1004036. Epub 2011 Apr 27.

Abstract

CD103(+) dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that a small number of cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11c(hi)CD11b(lo) DCs, CD11c(hi)CD11b(hi) DCs, CD11c(int)CD11b(int) macrophages, and CD11c(int)CD11b(hi) eosinophils. The CD11c(hi)CD11b(hi) DCs, which are CD103(+), specifically express TLR5 and induce the differentiation of naive B cells into IgA(+) plasma cells. These DCs also mediate the differentiation of Ag-specific Th17 and Th1 cells in response to flagellin. We found that small intestine CD103(+) DCs of the LP (LPDCs) could be divided into a small subset of CD8α(+) cells and a larger subset of CD8α(-) cells. Flow cytometry analysis revealed that CD103(+)CD8α(+) and CD103(+)CD8α(-) LPDCs were equivalent to CD11c(hi)CD11b(lo) and CD11c(hi)CD11b(hi) subsets, respectively. We analyzed a novel subset of CD8α(+) LPDCs to elucidate their immunological function. CD103(+)CD8α(+) LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-α, IL-10, or IL-23, following TLR ligand stimulation. CD103(+)CD8α(+) LPDCs did not express the gene encoding retinoic acid-converting enzyme Raldh2 and were not involved in T cell-independent IgA synthesis or Foxp3(+) regulatory T cell induction. Furthermore, CD103(+)CD8α(+) LPDCs induced Ag-specific IgG in serum, a Th1 response, and CTL activity in vivo. Accordingly, CD103(+)CD8α(+) LPDCs exhibit a different function from CD103(+)CD8α(-) LPDCs in active immunity. This is the first analysis, to our knowledge, of CD8α(+) DCs in the LP of the small intestine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • CD8 Antigens / immunology
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cytotoxicity, Immunologic / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Integrin alpha Chains / immunology
  • Integrin alpha Chains / metabolism
  • Interleukin-12 Subunit p40 / immunology
  • Interleukin-12 Subunit p40 / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestine, Small / immunology*
  • Intestine, Small / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology
  • Toll-Like Receptor 7 / metabolism
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / immunology
  • Toll-Like Receptor 9 / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism

Substances

  • Antigens, CD
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Integrin alpha Chains
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • alpha E integrins