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PMID: 10540214 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD40-deficient dendritic cells producing interleukin-10, but not interleukin-12, induce T-cell hyporesponsiveness in vitro and prevent acute allograft rejection.

Immunology ·Vol. 98 ·No. 2 ·1999-10-00 ·Pages 159-70

Gao JX, Madrenas J, Zeng W, Cameron MJ, Zhang Z, Wang JJ, Zhong R, Grant D

Abstract

The induction of an immune response or tolerance is mediated by corresponding subsets of dendritic cells (DC). However, the property of tolerogenic DC is not clear. Recently, we have characterized a population of CD11c+ splenic DC derived from long-term mixed leucocyte culture (LT-MLC), which are able to proliferate upon stimulation and have a strong primary mixed leucocyte reaction (MLR)-stimulating activity in conventional MLR. In this study, we show that, in contrast to the irradiated ones, non-irradiated LT-MLC-derived DC induce polyclonal antigen-specific T-cell hyporesponsiveness when cocultured with allogeneic splenocytes for 3-11 days. The degree of the hyporesponsiveness increased with the length of coculture. Although these DC expressed major histocompatibility complex class II and B7 costimulatory molecules, which are down-regulated during coculture, they expressed very low or undetectable CD40 before and after coculture, respectively. The CD40-deficient DC spontaneously produce interleukin-10 (IL-10), but not IL-12. The skewed balance between IL-10 and IL-12 is associated with their capability to induce T-cell hyporesponsiveness, because a neutralizing antibody to IL-10, exogenous recombinant IL-12 or lipopolysaccharide (LPS) significantly blocked the hyporesponsiveness. Accordingly, infusion of a small number of non-irradiated LT-MLC-derived DC (5x105) significantly prolonged the survival of a vascularized heterotopic murine heart transplant, whereas irradiated DC accelerated graft rejection. These data suggest that CD40-deficient DC producing IL-10, but not IL-12 can induce T-cell hyporesponsiveness in vitro and in vivo.

MeSH Terms
Adoptive Transfer Animals CD40 Antigens/immunology Cells, Cultured Dendritic Cells/immunology Flow Cytometry Graft Rejection/immunology Immune Tolerance Interleukin-10/immunology Interleukin-12/immunology Lipopolysaccharides/pharmacology Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL T-Lymphocytes/immunology Transplantation, Homologous
Chemicals
CD40 Antigens Lipopolysaccharides Interleukin-10 Interleukin-12
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gao J X
Transplantation and Immunobiology Group, The John P. Robarts Research Institute, London, Ont., Canada.
Madrenas J
Zeng W
Cameron M J
Zhang Z
Wang J J
Zhong R
Grant D
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Article Info
Journal
Immunology
Abbr.
Immunology
ISSN
0019-2805
DOI
10.1046/j.1365-2567.1999.00863.x
Published
1999-10-00
Pages
159-70
Language
English
Region
England
NLM ID
0374672
PMCID
PMC2326930
Subset
IM
External Links
PubMed source DOI: 10.1046/j.1365-2567.1999.00863.x PMC Full Text View journal details
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