The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4(+) T cells.

Abstract

Chemokines are involved in the regulation of leukocyte migration and for some of them, T-cell costimulation. To date, the only direct property of lymphotactin (Lptn), the unique member of the C class of chemokines, consists of T-cell chemoattraction. This report describes a novel function for Lptn in human T-lymphocyte biology, by demonstrating the direct ability of Lptn to both inhibit and costimulate CD4(+) and CD8(+) T-cell activation, respectively. Lptn but not RANTES inhibited CD4(+) T-cell proliferation, through a decreased production of Th1 (interleukin [IL]-2, interferon [IFN]-gamma) but not Th2 (IL-4, IL-13) lymphokines, and decreased IL-2R alpha expression. Transfections in Jurkat cells showed a Lptn-mediated transcriptional down-regulation of gene-promoter activities specific for Th1-type lymphokines, as well as of nuclear factor of activated T cells (NF-AT) but not AP-1 or NF-KB enhancer activities. This suppressive action of Lptn could be compensated by overexpression of NF-ATc but not NF-ATp. CD4(+) T-cell proliferation was completely restored by exogenous IL-2 or reversed by pertussis toxin, wortmannin, and genistein, suggesting the involvement of multiple partners in Lptn signaling. In contrast to CD4(+) cells, Lptn exerted a potent costimulatory activity on CD8(+) T-cell proliferation and IL-2 secretion. These data provide important insights into the role of Lptn in differential regulation of normal human T-cell activation and its possible implication in immune response disorders. (Blood. 2000;96:420-428)

Extracted Key Phrases

10 Figures and Tables

0100200'02'04'06'08'10'12'14'16
Citations per Year

364 Citations

Semantic Scholar estimates that this publication has 364 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Cerdn2000TheCC, title={The C-class chemokine, lymphotactin, impairs the induction of Th1-type lymphokines in human CD4(+) T cells.}, author={Carlos R. Cerd{\'a}n and E. Serfling and Daniel Olive}, journal={Blood}, year={2000}, volume={96 2}, pages={420-8} }