Monoclonal anti-CD44 antibody acts in synergy with anti-CD2 but inhibits anti-CD3 or T cell receptor-mediated signaling in murine T cell hybridomas.
We investigated the effects of anti-murine CD44 monoclonal antibodies on the activation of antigen-specific T cell hybridomas. Anti-murine CD44 antibodies by themselves did not induce the production of IL-2 by antigen-specific T cell hybridomas. However, anti-murine CD44 monoclonal antibodies were able to either inhibit or enhance the production of IL-2, depending on the other monoclonal antibodies used as comitogenic stimuli. When a T cell hybridoma was activated by antigen and antigen-presenting cells or anti-CD3 antibodies, addition of anti-CD44 antibodies inhibited IL-2 production. In contrast, monoclonal anti-CD44 antibodies acted in synergy with anti-human CD2 antibodies in stimulating a murine T cell hybridoma stably transfected with the human CD2 gene to produce IL-2. Therefore, cross-linking of surface CD44 is able to deliver either a positive or a negative signal in murine antigen-specific T cell hybridomas. One of the ligands for CD44 is hyaluronic acid. Hyaluronic acid in vitro significantly increased the activation of murine T cell hybridomas. Hyaluronic acid itself was mitogenic for T cell hybridomas. Therefore, in addition to being an adhesion molecule, CD44 functions as a signal-transducing molecule on murine T cell hybridomas.
Guo
Y J
YJ
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Ma
J
J
Wong
J H
JH
Lin
S C
SC
Chang
H C
HC
Bigby
M
M
Sy
M S
MS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D018801:CD2 Antigens; D017252:CD3 Complex / Q000276:immunology*; D004357:Drug Synergism; D006801:Humans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid / Q000494:pharmacology; D006825:Hybridomas / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D015398:Signal Transduction; D014162:Transfection
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D006820:Hyaluronic Acid