Abstract
Previous studies have shown that the CXC chemokine, IFN-gamma-inducible T cell alpha chemoattractant (I-TAC), was chemotactic for IL-2-activated human T lymphocytes, which express abundant CXCR3. However, because most memory T lymphocytes are also CXCR3(+), the ability of I-TAC to promote the migration of normal human blood T cells across HUVEC monolayers in Transwell chambers was examined. I-TAC induced a marked (4- to 6-fold) increase in transendothelial migration (TEM) of T cells across unstimulated HUVEC from 5.6 to 28% of input T cells and was substantially more active than IFN-gamma-inducible protein-10, another CXCR3 ligand. I-TAC significantly enhanced TEM of T cells across TNF-alpha, but not across IFN-gamma or IFN-gamma plus TNF-alpha-activated HUVEC. IFN-gamma or IFN-gamma plus TNF-alpha-activated HUVEC produced substantial amounts of I-TAC, in contrast to TNF-alpha-treated EC. Both CD4(+) and CD8(+) T cells migrated in response to I-TAC to a similar extent, while memory T cells migrated several fold better than naive T cells. Blockade of LFA-1 strongly inhibited I-TAC-induced T cell TEM across unstimulated HUVEC, and approximately 50-60% of the TEM across cytokine-activated HUVEC. However, blocking both LFA-1 and very late Ag-4 abolished I-TAC induced T cell TEM. In vivo significant levels of I-TAC were detected in arthritic synovial fluid. Thus, I-TAC is one of the most potent chemoattractants of normal human blood CD4 and CD8 T cell TEM and is likely a major mediator of blood memory T lymphocyte migration to inflammation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Blocking / pharmacology
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Movement / immunology
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Cells, Cultured
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Chemokine CXCL11
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Chemokines, CXC / metabolism
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Chemokines, CXC / physiology*
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Chemotaxis, Leukocyte / immunology*
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Cytokines / pharmacology
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Diffusion Chambers, Culture
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / immunology*
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Endothelium, Vascular / metabolism
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Humans
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Immunologic Memory
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Integrin alpha4beta1
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Integrins / antagonists & inhibitors
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Integrins / physiology
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Interferon-gamma / blood
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Interferon-gamma / physiology*
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Interleukin-2 / pharmacology
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Interphase / immunology
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Lymphocyte Function-Associated Antigen-1 / immunology
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Lymphocyte Function-Associated Antigen-1 / physiology
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Osteoarthritis / immunology
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Osteoarthritis / metabolism
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Receptors, Lymphocyte Homing / antagonists & inhibitors
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Receptors, Lymphocyte Homing / physiology
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Synovial Fluid / immunology
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Synovial Fluid / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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Tumor Necrosis Factor-alpha / physiology*
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Umbilical Veins
Substances
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Antibodies, Blocking
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CXCL11 protein, human
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Chemokine CXCL11
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Chemokines, CXC
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Cytokines
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Integrin alpha4beta1
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Integrins
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Interleukin-2
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Lymphocyte Function-Associated Antigen-1
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Receptors, Lymphocyte Homing
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Tumor Necrosis Factor-alpha
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Interferon-gamma