The Journal of Immunology, Vol 150, Issue 10 4292-4302, Copyright © 1993 by American Association of Immunologists

ARTICLES

Regulated expression of a receptor for hyaluronan-mediated motility on human thymocytes and T cells

LM Pilarski, H Miszta and EA Turley
Department of Immunology, University of Alberta, Edmonton, Canada.

A receptor for hyaluronan-mediated motility (RHAMM) has been shown to promote cell locomotion. Among human T lineage lymphocytes, RHAMM is expressed only on a subset of thymocytes, being absent on mature peripheral T cells from blood, spleen, and lymph node. Among thymocytes, RHAMM is selectively expressed on a subset of CD3+ CD45RA+R0+ cells, and functions in motility as shown by the ability of anti-RHAMM to reduce the speed of thymocyte locomotion from 11 microns/minute to 3 microns/min. Although freshly isolated multi- negative (MN) thymocytes (CD3-4-8-19-) lack RHAMM, its expression is induced on day 3 of culture in a variety of conditions that support differentiation, as assessed by acquisition of CD3. When MN thymocytes are cultured on plates coated with fibronectin, expression of RHAMM is prolonged, but on uncoated surfaces, its expression is transient and lost by day 7 of culture with PHA or IL-2. Culture of MN thymocytes on thymic epithelial layers, with or without IL-2, resulted in a lack of RHAMM expression. Because in the absence of epithelial cells, RHAMM is expressed, the effect appears to be one of inhibition. Although expression of RHAMM by MN thymocytes cultured with IL-2 on uncoated surfaces is transient, addition of cyclosporin A resulted in prolonged expression. These observations are consistent with the view that cyclosporin A inactivates a RHAMM-directed inhibitory mechanism. Mature peripheral blood T cells transiently express RHAMM upon culture with PHA, PMA, or IL-2. T cells that expressed RHAMM after culture with PMA alone lacked RHAMM when stimulated by mitogenic CD2 antibodies with or without CD28 antibody, indicating inhibition of RHAMM expression. Thus expression of RHAMM is regulated by a RHAMM-directed inhibitory mechanism induced by stimulation through CD2/CD28. A similar mechanism may operate in thymocyte/epithelial cell cultures. These results suggest the inhibition of RHAMM during early, presumably sessile, thymic progenitor development, followed by its induction during developmental stages when locomotion is required. The apparently strong negative regulatory control over RHAMM expression by microenvironmental factors and by known thymic and T cell signaling molecules supports this view.

This article has been cited by other articles:

				L. M. Pilarski, E. Pruski, J. Wizniak, D. Paine, K. Seeberger, M. J. Mant, C. B. Brown, and A. R. Belch Potential Role for Hyaluronan and the Hyaluronan Receptor RHAMM in Mobilization and Trafficking of Hematopoietic Progenitor Cells Blood, May 1, 1999; 93(9): 2918 - 2927. [Abstract] [Full Text] [PDF]

				M. Crainie, A. R. Belch, M. J. Mant, and L. M. Pilarski Overexpression of the Receptor for Hyaluronan-Mediated Motility (RHAMM) Characterizes the Malignant Clone in Multiple Myeloma: Identification of Three Distinct RHAMM Variants Blood, March 1, 1999; 93(5): 1684 - 1696. [Abstract] [Full Text] [PDF]

				V Assmann, D Jenkinson, J. Marshall, and I. Hart The intracellular hyaluronan receptor RHAMM/IHABP interacts with microtubules and actin filaments J. Cell Sci., January 11, 1999; 112(22): 3943 - 3954. [Abstract] [PDF]

				S. Zhang, M. C. Y. Chang, D. Zylka, S. Turley, R. Harrison, and E. A. Turley The Hyaluronan Receptor RHAMM Regulates Extracellular-regulated Kinase J. Biol. Chem., May 1, 1998; 273(18): 11342 - 11348. [Abstract] [Full Text] [PDF]

				V Assmann, J. Marshall, C Fieber, M Hofmann, and I. Hart The human hyaluronan receptor RHAMM is expressed as an intracellular protein in breast cancer cells J. Cell Sci., January 6, 1998; 111(12): 1685 - 1694. [Abstract] [PDF]

				R. C. Savani, G. Cao, P. M. Pooler, A. Zaman, Z. Zhou, and H. M. DeLisser Differential Involvement of the Hyaluronan (HA) Receptors CD44 and Receptor for HA-mediated Motility in Endothelial Cell Function and Angiogenesis J. Biol. Chem., September 21, 2001; 276(39): 36770 - 36778. [Abstract] [Full Text] [PDF]