CD44 contributes to T cell activation.
We demonstrate here that the CD44 molecule, which mediates lymphocyte adhesion to high endothelial venules (HEV), is also involved in the delivery of an activation signal to the T cell. We have produced a CD44 mAb (H90) which is able to block the binding of lymphocytes to high endothelial venules. H90 had no effect on [3H]TdR incorporation of whole PBL stimulated by lectins, allogeneic cells, or CD3 mAb in the soluble phase; in contrast, it strongly increased [3H]TdR incorporation of PBL stimulated by CD2 pairs of mAb or by CD3 mAb linked to the plastic culture plates, when purified T cells were used, H90 mAb could efficiently induce them to proliferate after a primary signal of activation delivered via cross-linked CD3 or via CD2, an effect mediated by Il-2 synthesis and Il-2R expression. Thus, the effect of H90 mAb resembles the mitogenic effect of CD28 "9.3" mAb. However, several results show that CD28 and CD44 mediate different signals to the T cells: i) in contrast to CD28 mAb, CD44 mAb cannot complement the signal delivered by a soluble CD3 mAb, lectins, or PMA; ii) CD44 mAb, at the difference of CD28 mAb, cannot induce CD3+ thymocytes to proliferate in conjunction with a first signal provided via cross-linked CD3 or via CD2; iii) F(ab) fragments of H90 were efficient, whereas divalent fragments of CD29 9.3 mAb are required to produce activation signals; and iv) CD44 and CD28 mAb produce a very strong synergistic effect on T cell proliferation. These results fit with previous ones showing that endothelial cells can play the role of accessory cell in T cell activation and that a hierarchy of signaling can be delivered to T cells via CD3 and CD2.
Huet
S
S
Laboratoire d'Immunologie des Tumeurs de l'Enfant, Institut Gustave-Roussy, Villejuif, France.
Groux
H
H
Caillou
B
B
Valentin
H
H
Prieur
A M
AM
Bernard
A
A
D000276:Adjuvants, Immunologic / Q000276:immunology / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology* / Q000302:isolation & purification; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D018801:CD2 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008970:Molecular Weight; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D016201:Receptors, Lymphocyte Homing; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7