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Prepublished online as a Blood First Edition Paper on August 15, 2002; DOI 10.1182/blood-2002-03-0697.
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Blood, 1 January 2003, Vol. 101, No. 1, pp. 216-225
IMMUNOBIOLOGY
Differential chemokine expression profiles in human peripheral
blood T lymphocytes: dependence on T-cell coreceptor and
calcineurin signaling
Anthony D. Cristillo,
Mirtha J. Macri, and
Barbara E. Bierer
From the Laboratory of Lymphocyte Biology, National
Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, MD.
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)-1 , and MIP-1 were all rapidly induced
and sensitive to cyclosporine treatment. At later time points, the
expression of MIP-1 and MIP-1, 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.
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