PMID- 20083662
OWN - NLM
STAT- MEDLINE
DCOM- 20100326
LR  - 20201215
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 4
DP  - 2010 Feb 15
TI  - Tolerogenic dendritic cells generated with different immunosuppressive cytokines 
      induce antigen-specific anergy and regulatory properties in memory CD4+ T cells.
PG  - 1765-75
LID - 10.4049/jimmunol.0902133 [doi]
AB  - Dendritic cells (DCs) are professional APCs involved in the initiation of both 
      immunity and immunological tolerance. In autoimmune diseases or graft rejections, 
      most reactive lymphocytes are effector/memory cells. It is believed that memory T 
      cells are more resistant to tolerance induction than naive lymphocytes; however, 
      studies on mechanisms for their efficient tolerization are still scarce. In this 
      study, we generated human monocyte-derived DCs by culture with GM-CSF and IL-4 
      (control DCs), as well as tolerogenic DCs (tDCs) by adding IL-10, 
      IL-10/TGF-beta1, or IL-10/IL-6. Cells were maturated with TNF-alpha/PGE(2). 
      Compared with control DCs, tDCs had similar expression of HLA-DR, CD80, and CD86, 
      lower expression of CD40, higher levels of macrophage markers, enhanced endocytic 
      ability, increased secretion of IL-6, IL-10 (only tDCs generated with IL-10 and 
      tDCs generated with IL-10/IL-6), and PGE(2), and lower secretion of IL-12 and 
      IL-23. In vitro, tDCs had the capacity to induce anergy in tetanus 
      toxoid-specific memory CD4(+) T cells, whereas the proliferative response to an 
      unrelated Ag was intact. Anergy could be reverted upon exposure to IL-2. 
      tDC-primed T cells have low suppressive ability. Nevertheless, the generation of 
      both anergic and regulatory T cells was more efficient with tDCs generated with 
      IL-10/TGF-beta1. Microarray-based gene expression profiling reflected modulated 
      expression of several transcripts in tDCs. Surface CLIP-HLA-DR complexes and 
      intracellular thrombospondin-1 were increased in the three tDCs. CD39 was highly 
      expressed only in tDC-TGF, which correlated with increased adenosine production. 
      We propose that these molecules, together with IL-10 and prostanoids, are key 
      factors to induce Ag-specific tolerance in memory T cells.
FAU - Torres-Aguilar, Honorio
AU  - Torres-Aguilar H
AD  - Department of Molecular Biomedicine, Centro de Investigacion y de Estudios 
      Avanzados del Instituto Politecnico Nacional, Mexico City, Mexico.
FAU - Aguilar-Ruiz, Sergio R
AU  - Aguilar-Ruiz SR
FAU - Gonzalez-Perez, Gabriela
AU  - Gonzalez-Perez G
FAU - Munguia, Rosario
AU  - Munguia R
FAU - Bajana, Sandra
AU  - Bajana S
FAU - Meraz-Rios, Marco A
AU  - Meraz-Rios MA
FAU - Sanchez-Torres, Carmen
AU  - Sanchez-Torres C
LA  - eng
SI  - GEO/GSE18921
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100118
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antigens, Differentiation, B-Lymphocyte)
RN  - 0 (Cytokines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (IL10 protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thrombospondin 1)
RN  - 0 (invariant chain)
RN  - 130068-27-8 (Interleukin-10)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Antigens, Differentiation, B-Lymphocyte/physiology
MH  - CD4-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cell Differentiation/*immunology
MH  - Cells, Cultured
MH  - Clonal Anergy/immunology
MH  - Cytokines/*physiology
MH  - Dendritic Cells/classification/*immunology/*metabolism
MH  - Dinoprostone/physiology
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Histocompatibility Antigens Class II/physiology
MH  - Humans
MH  - *Immune Tolerance
MH  - *Immunologic Memory
MH  - Immunosuppressive Agents/pharmacology
MH  - Interleukin-10/physiology
MH  - Macrophages/classification/immunology/metabolism
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
MH  - Thrombospondin 1/physiology
EDAT- 2010/01/20 06:00
MHDA- 2010/03/27 06:00
CRDT- 2010/01/20 06:00
PHST- 2010/01/20 06:00 [entrez]
PHST- 2010/01/20 06:00 [pubmed]
PHST- 2010/03/27 06:00 [medline]
AID - jimmunol.0902133 [pii]
AID - 10.4049/jimmunol.0902133 [doi]
PST - ppublish
SO  - J Immunol. 2010 Feb 15;184(4):1765-75. doi: 10.4049/jimmunol.0902133. Epub 2010 
      Jan 18.