Differential chemokine expression profiles in human peripheral blood T lymphocytes: dependence on T-cell coreceptor and calcineurin signaling

The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues....

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Bibliographic Details
Published in:Blood 2003-01, Vol.101 (1), p.216-225
Main Authors: Cristillo, Anthony D., Macri, Mirtha J., Bierer, Barbara E.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood Cells
Calcineurin - physiology
CD28 Antigens - physiology
Chemokine CCL3
Chemokine CCL4
Chemokine CXCL10
Chemokines - genetics
Chemokines, C
Chemokines, CXC - genetics
Cyclosporine - pharmacology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Regulation
Humans
Immunobiology
Interleukin-8 - genetics
Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation
Lymphokines - genetics
Macrophage Inflammatory Proteins - genetics
RNA, Messenger - analysis
Sialoglycoproteins - genetics
Signal Transduction
T-Lymphocytes - metabolism
Transcriptional Activation
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Summary:The chemokine superfamily consists of small (8-10 kDa) molecules that function to attract, selectively, different subsets of leukocytes. Binding of chemokines to their appropriate G-protein–coupled receptors is necessary for primary immune responses and for homing of leukocytes to lymphoid tissues. Here, we have characterized the signaling pathways in primary T lymphocytes that regulate chemokine gene induction using an RNase protection assay. Dependence on stimulation through the coreceptor CD28 and sensitivity to the calcineurin inhibitors cyclosporine and tacrolimus were studied using purified human peripheral blood lymphocytes. Lymphotactin (Ltn), macrophage inflammatory protein (MIP)–1α, and MIP-1β were all rapidly induced and sensitive to cyclosporine treatment. At later time points, the expression of MIP-1α and MIP-1β, but not of Ltn, was restored despite the inhibition of calcineurin activity. By contrast, the induction of interleukin-8 was delayed and was found to be cyclosporine insensitive. Calcineurin activity of IP-10 mRNA induction was contingent on the specific T-cell stimulation conditions, suggesting that IP-10 expression is modulated by calcineurin-dependent and -independent signaling pathways. Differential chemokine expression profiles result from the engagement of T-cell coreceptors and the requirement for, and the dependence on, calcineurin phosphatase activity.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2002-03-0697