Dm. Sansom et al., B7 CD28 BUT NOT LFA-3/CD2 INTERACTIONS CAN PROVIDE 3RD-PARTY CO-STIMULATION FOR HUMAN T-CELL ACTIVATION/, Immunology, 80(2), 1993, pp. 242-247
The requirement for co-stimulation in T-cell activation has become fir
mly 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 condit
ions using transfected Chinese hamster ovary cells. Using anti-CD3 ant
ibodies we observed that B7 but not LFA-3 transfectants were capable o
f co-stimulating proliferation in purified peripheral blood T cells. I
n addition, both LFA-3 and B7 could induce proliferation in response t
o phytohaemagglutinin (PHA) and we obtained additive effects using bot
h B7 and LFA-3 together. Using the superantigen staphylococcal enterot
oxin B (SEB), we observed that presentation to purified T cells requir
ed the presence of class II-positive transfectants and that sensitivit
y to antigen was increased approximately 100-fold by the co-transfecti
on of either B7 or LFA-3. However, when co-stimulatory molecules were
provided by cells separate from those engaging the T-cell receptor (Tc
R), only B7 was capable of enhancing proliferation. Kinetic studies wh
ich investigated the time dependence for co-stimulation revealed that
T cells responding to anti-CD3 antibodies required the B7 co-stimulati
on 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 prolifera
tion.