B7/CD28 but not LFA-3/CD2 interactions can provide 'third-party' co-stimulation for human T-cell activation.
The requirement for co-stimulation in T-cell activation has become firmly established, whilst the precise identity of the molecules involved remains uncertain. Some of the major co-stimulatory molecules include ICAM-1, LFA-3 and B7. We have investigated the abilities of both LFA-3 and B7 to co-stimulate T-cell proliferation under a number of conditions using transfected Chinese hamster ovary cells. Using anti-CD3 antibodies we observed that B7 but not LFA-3 transfectants were capable of co-stimulating proliferation in purified peripheral blood T cells. In addition, both LFA-3 and B7 could induce proliferation in response to phytohaemagglutinin (PHA) and we obtained additive effects using both B7 and LFA-3 together. Using the superantigen staphylococcal enterotoxin B (SEB), we observed that presentation to purified T cells required the presence of class II-positive transfectants and that sensitivity to antigen was increased approximately 100-fold by the co-transfection of either B7 or LFA-3. However, when co-stimulatory molecules were provided by cells separate from those engaging the T-cell receptor (TcR), only B7 was capable of enhancing proliferation. Kinetic studies which investigated the time dependence for co-stimulation revealed that T cells responding to anti-CD3 antibodies required the B7 co-stimulation within the first few hours, for proliferation to be effective. Our data differentiate between the co-stimulatory abilities of B7 and LFA-3 and support the concept of a pivotal role for B7 in T-cell proliferation.
Sansom
D M
DM
Bath Institute for Rheumatic Diseases, Trim Bridge, U.K.
Wilson
A
A
Boshell
M
M
Lewis
J
J
Hall
N D
ND
D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology*; D018801:CD2 Antigens; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014162:Transfection
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018801:CD2 Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic