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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2001-12-0196.
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Blood, 1 July 2002, Vol. 100, No. 1, pp. 11-16
CHEMOKINES
Trafficking machinery of NKT cells: shared and differential
chemokine receptor expression among
V 24+V 11+ NKT cell subsets with distinct
cytokine-producing capacity
Chang H. Kim,
Brent Johnston, and
Eugene C. Butcher
From the Laboratory of Immunology and Vascular Biology,
Department of Pathology, Stanford University School of Medicine, CA;
and Center for Molecular Biology and Medicine, Veterans Affairs Palo
Alto Health Care System, CA.
Natural killer T (NKT) cells are important regulators of the immune
system, but their trafficking machinery, including expression of
chemokine receptors, has been poorly defined. Unlike other conventional
T-cell populations, we show that most NKT cells express receptors for
extralymphoid tissue or inflammation-related chemokines (CCR2, CCR5,
and CXCR3), while few NKT cells express lymphoid tissue-homing
chemokine receptors (CCR7 and CXCR5). A population with homing
potential for lymph nodes (L selectin+ CCR7+)
exists only within a small subset of CD4 NKT cells. We show differential expression of chemokine receptors among NKT cell subsets:
CCR4 is mainly expressed by a high cytokine
(interleukin-4/interleukin-2)-producing (CD4) NKT subset, while CCR1,
CCR6, and CXCR6 are preferentially expressed by the low
cytokine-producing CD8 and CD4 CD8 subsets.
In line with this, TARC/CCL17 (a CCR4 ligand) induces preferential
chemotaxis of the CD4 NKT subset, while chemotactic activities of
LARC/CCL20 (a CCR6 ligand) and MIP-1 /CCL3 (a CCR1 ligand) are
focused on the CD8 and CD4 CD8 NKT cells. We
conclude that, unlike conventional naive, memory, or effector T cells,
the entire NKT cell population expresses nonlymphoid tissue homing
chemokine receptors, yet NKT cell subsets differ considerably from each
other by displaying distinct and reciprocal expression patterns of some
chemokine receptors. Our results identify chemokine receptors that are
potentially important for trafficking of human blood NKT cell subsets
and reveal their function (cytokine production capacity)-dependent
differential trafficking potentials.

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