HELPER EFFECTOR FUNCTION OF HUMAN T-CELLS STIMULATED BY ANTI-CD3 MAB CAN BE ENHANCED BY COSTIMULATORY SIGNALS AND IS PARTIALLY DEPENDENT ONCD40-CD40 LIGAND INTERACTION
J. Kwekkeboom et al., HELPER EFFECTOR FUNCTION OF HUMAN T-CELLS STIMULATED BY ANTI-CD3 MAB CAN BE ENHANCED BY COSTIMULATORY SIGNALS AND IS PARTIALLY DEPENDENT ONCD40-CD40 LIGAND INTERACTION, European Journal of Immunology, 24(3), 1994, pp. 508-517
In this study we have investigated whether anti-CD3-induced human T ce
ll help for immunoglobulin production could be enhanced by co-stimulat
ion of the T cells via other T cell surface molecules, and the contrib
ution of CD40-CD40 ligand interaction to the execution of T helper eff
ector function induced by these different stimulatory signals. In a sy
stem in which irradiated tonsillar T cells were stimulated with immobi
lized anti-CD3 monoclonal antibody (mAb); it was found that ligation o
f CD2 with a mitogenic pair of mAb considerably enhanced anti-CD3-indu
ced T cell help for immunoglobulin production. Likewise, ligation of C
D28 with mAb enhanced T helper activity, although to a lesser extent.
Upon addition of anti-CD28 and anti-CD2 mAb together, an even higher i
mmunoglobulin production was observed. This combination resulted in a
four- to fivefold increase in immunoglobulin production as compared to
cultures in which T cells were stimulated with anti-CD3 mAb alone. Th
e effect of ligation with B7, the natural ligand of CD28, was studied
in a system which utilizes the presentation of anti-CD3 mAb on human F
c gamma RII-expressing mouse fibroblasts which were co-transfected wit
h human B7. It appeared that B7 could stimulate help for immunoglobuli
n production much more efficiently than ligation of CD28 with mAb did.
Physical separation of B cells from T cells led to complete abrogatio
n of immunoglobulin production. Blocking of CD40 with specific mAb, wh
ich have no intrinsic B cell stimulatory properties, or the CD40 ligan
d with a soluble CD40-human IgM fusion protein, resulted in dose-depen
dent, but only partial, inhibition of T cell-dependent immunoglobulin
production with all modes of T cell activation tested. A clear correla
tion was found between the induction of CD40 ligand expression on the
T cells by the different modes of co-stimulation and subsequent immuno
globulin production by the B cells. It is concluded that ligation of C
D28 and/or CTLA-4, and of CD2 can generate co-stimulatory signals for
T cell help for immunoglobulin production, which was found to be only
partially dependent on the CD40-CD40 ligand interaction.