Hyaluronate is costimulatory for human T cell effector functions and binds to CD44 on activated T cells.
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.
Galandrini
R
R
Department of Clinical Medicine, Pathology, and Pharmacology, University of Perugia, Italy.
Galluzzo
E
E
Albi
N
N
Grossi
C E
CE
Velardi
A
A
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D006820:Hyaluronic Acid