Hyaluronate is costimulatory for human T cell effector functions and binds to CD44 on activated T cells

J Immunol. 1994 Jul 1;153(1):21-31.


Lymphohematopoiesis, cell matrix adhesion, homing of leukocytes, T cell activation, and tumor metastasis are mediated through the CD44 family of cell surface receptors. We have recently shown that anti-CD44 mAb trigger protein tyrosine kinase-dependent activation of T cell effector functions. Here, we show that hyaluronate (HA), a CD44 ligand, in conjunction with CD3/TCR-mediated stimuli, is costimulatory for human peripheral blood T cell proliferation, for IL-2 production by Th clones, and for release of trypsin-like esterase by cytolytic T cell clones. A human T cell line, HUT-78, was found to bind HA and on HA coating it was used as a target for cytolytic T cell clones. After anti-CD3 stimulation, CD3+/CD8+ clones acquire the ability of lysing HA-coated HUT-78 cells more efficiently than the same HA-uncoated targets. Resting peripheral blood T cells and T cell clones do not adhere to HA-coated plates. However, 24-h anti-CD3 mAb stimulation gives them the transient ability to bind HA. HA adhesion of activated T cells and T cell clones, as well as that of T cell lines, is blocked by one anti-CD44 mAb (J-173). Two other anti-CD44 mAbs induce a 10-fold increase in HA adhesiveness of anti-CD3-stimulated peripheral blood T cells. This impressive HA adhesiveness is also readily blocked by J-173 anti-CD44 mAb. These data indicate that 1) HA is costimulatory for human T cell effector functions in conjunction with CD3/TCR-mediated stimuli, 2) the capacity to bind HA is acquired by resting T cells and T cell clones after anti-CD3 stimulation, and 3) HA binding occurs via specific interaction with CD44 molecules expressed on activated T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • Carrier Proteins / metabolism*
  • Cell Adhesion / drug effects
  • Humans
  • Hyaluronan Receptors
  • Hyaluronic Acid / metabolism
  • Hyaluronic Acid / pharmacology*
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • Receptors, Cell Surface / metabolism*
  • Receptors, Lymphocyte Homing / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Helper-Inducer / drug effects


  • Carrier Proteins
  • Hyaluronan Receptors
  • Interleukin-2
  • Receptors, Cell Surface
  • Receptors, Lymphocyte Homing
  • Hyaluronic Acid