Macrophage inflammatory protein-1 beta induces migration and activation of human thymocytes

Dairaghi, D. J.; Franz-Bacon, K.; Callas, E.; Cupp, J.; Schall, T. J.; Tamraz, S. A.; Boehme, S. A.; Taylor, N.; Bacon, K. B.


1998-04-15 / vol 91 / pages 2905-2913


The CC chemokine macrophage inflammatory protein 1 beta (MIP-1 beta), has been shown to be a chemoattractant preferentially activating CD4(+) CD45RA(+) T lymphocytes, Further analysis of chemokine action on lymphocytic cells has shown the potent migration-promoting capacity of MIP-1 beta on human thymocytes. The responding cells were the CD4(+) and CD8(+) single-positive (SP), as well as the CD4(+) CD8(+) double-positive (DP) populations, with little if any migratory activity on the double-negative (DN) population. The activation of thymocytes by MIP-1 beta appeared to be a direct, receptor-mediated event as evidenced by the rapid mobilization of intracellular calcium, increase in proteins phosphorylated on tyrosine, and activation of the mitogen-activated protein kinase (MAPK) pathway. Radioligand binding analyses showed specific and displaceable binding of MIP-1 beta to thymocytes with a Kd of approximately 1 nmol/L, a profile that was comparable with MIP-1 beta binding to CCR-5-transfected NIH 3T3 cells. In addition, CCR-5 mRNA was detected in total thymocyte populations indicating that activation of thymocytes by MIP-1 beta may occur through binding to CCR-5. Further dissection of the subpopulations showed that only the DP and CD8(+) SP populations expressed CCR-5 and expression data on these two populations was confirmed using anti-CCR-5 monoclonal antibody. These data may be suggestive of a role for MIP-1 beta in human thymocyte activation, and show a potential route for HIV infectivity in the developing immune system. (C) 1998 by The American Society of Hematology.



molecular-cloning; t-cells; cytokine; chemokine receptor; functional expression; hiv-1; lymphotactin; mip-1-alpha; mip-1-beta; rantes

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