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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2003-5-21
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pubmed:abstractText |
Common variable immunodeficiency (CVID) is a heterogeneous group of B cell deficiency syndromes. T cell abnormalities are present in a high proportion of patients with CVID, suggesting impaired T cell-mediated stimulation of B cells. Based on the importance of IL-10 for B cell function and the involvement of the cAMP/protein kinase A type I (PKAI) system in IL-10 synthesis, we examined IL-10 secretion in T cells from CVID patients and controls, particularly focusing on possible modulatory effects of the cAMP/PKAI system. Our main findings were: 1) anti-CD3 and anti-CD3/anti-CD28 activated T cells from CVID patients secreted less IL-10 than healthy controls. This defect was not related to varying proportions of T cell subsets (e.g., CD4(+)/CD8(+), CD45RA(+)/RO(+), or CD28(-) T cells); 2) PKAI activation through the cAMP agonist 8-CPT-cAMP markedly inhibited IL-10 secretion from T cells through CD3 and CD28 activation in both patients and controls, but the sensitivity for cAMP-dependent inhibition was increased in CVID; 3) selective PKAI inhibition by Rp-8-Br-cAMPS markedly increased IL-10 secretion in anti-CD3 and anti-CD3/anti-CD28-stimulated T cells in both patients and controls. Even at the lowest concentrations of Rp-8-Br-cAMPS, IL-10 secretion in CVID patients reached levels comparable to those in controls. Our findings suggest impaired secretion of IL-10 by T cells from CVID patients, suggesting a possible link between T cell deficiency and impaired B cell function in CVID. The involvement of the cAMP/PKAI system in this defect suggests a novel target for therapeutic immunomodulation in CVID.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/8-bromoadenosine-3',5'-cyclic...,
http://linkedlifedata.com/resource/pubmed/chemical/8-cyclopentyl-1,3-dimethylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/PRKAR1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Theophylline,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5772-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12759461-8-Bromo Cyclic Adenosine Monophosphate,
pubmed-meshheading:12759461-Adolescent,
pubmed-meshheading:12759461-Adult,
pubmed-meshheading:12759461-Antigens, CD45,
pubmed-meshheading:12759461-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12759461-Cells, Cultured,
pubmed-meshheading:12759461-Child,
pubmed-meshheading:12759461-Child, Preschool,
pubmed-meshheading:12759461-Common Variable Immunodeficiency,
pubmed-meshheading:12759461-Cyclic AMP,
pubmed-meshheading:12759461-Cyclic AMP-Dependent Protein Kinase RIalpha Subunit,
pubmed-meshheading:12759461-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:12759461-Down-Regulation,
pubmed-meshheading:12759461-Female,
pubmed-meshheading:12759461-Humans,
pubmed-meshheading:12759461-Interleukin-10,
pubmed-meshheading:12759461-Lymphocyte Activation,
pubmed-meshheading:12759461-Male,
pubmed-meshheading:12759461-Middle Aged,
pubmed-meshheading:12759461-Protein Subunits,
pubmed-meshheading:12759461-T-Lymphocyte Subsets,
pubmed-meshheading:12759461-Theophylline,
pubmed-meshheading:12759461-Thionucleotides,
pubmed-meshheading:12759461-Up-Regulation
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pubmed:year |
2003
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pubmed:articleTitle |
Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency--involvement of protein kinase A type I.
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pubmed:affiliation |
Research Institute for Internal Medicine, National Hospital, Oslo, Norway. a.m.holm@klinmed.uio.no
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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