Regulation of human natural killer cell migration and proliferation by the exodus subfamily of CC chemokines

被引:44
作者
Robertson, MJ
Williams, BT
Christopherson, K
Brahmi, Z
Hromas, R
机构
[1] Indiana Univ, Med Ctr, Sch Med, Bone Marrow Transplantat Program, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Div Hematol Oncol, Dept Med, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA
[4] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
关键词
D O I
10.1006/cimm.1999.1601
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Natural killer (NR) cells play an important role in innate and adaptive immune responses to obligate intracellular pathogens. Nevertheless, the regulation of NK cell trafficking and migration to inflammatory sites is poorly understood. Exodus-1/MIP-3 alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP-3 beta/ELC/CK beta-11 are CC chemokines that share a unique aspartate-cysteine-cysteine-leucine motif near their amino terminus and preferentially stimulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectable chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 and -3 stimulated migration of polyclonal activated peripheral blood NK cells in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Exodus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodus-1, -2, and -3 did not induce NK; cell proliferation in the absence of other stimuli. Nevertheless, Exodus-2 and -3 significantly augmented ILS-induced proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-l, -2, and -3 did not affect the cytolytic activity of resting or activated peripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NH cells and NRL cells but not resting NK cells. Taken together, these results indicate that Exodus-2 and -3 can participate in the recruitment and proliferation of activated NH cells. Exodus-2 and -3 may regulate interactions between T cells and NK cells that are crucial for the generation of optimal immune responses, (C) 2000 Academic Press.
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页码:8 / 14
页数:7
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