SPECIFIC-INHIBITION OF T-LYMPHOCYTE COACTIVATION BY TRIGGERING INTEGRIN BETA(1), REVEALS CONVERGENCE OF BETA(1), BETA(2), AND BETA(7), SIGNALING PATHWAYS
Dg. Woodside et al., SPECIFIC-INHIBITION OF T-LYMPHOCYTE COACTIVATION BY TRIGGERING INTEGRIN BETA(1), REVEALS CONVERGENCE OF BETA(1), BETA(2), AND BETA(7), SIGNALING PATHWAYS, The Journal of immunology, 157(2), 1996, pp. 700-706
T cell coactivation is a dynamic process subject to integrin-dependent
positive and negative regulation. Costimulation of human peripheral b
lood T cells by CD3 mAb OKT3 in conjunction with anti-alpha(4) has bee
n shown to be down-regulated by the anti-beta(1.1) epitope-specific mA
b 18D3. As expected, maximal costimulation induced by alpha(4)-specifi
c mAb L25 was inhibited (70%) by the addition of soluble mAb 18D3. Sur
prisingly, soluble mAb 18D3 inhibited maximal proliferation induced by
the costimulatory alpha(4) beta(7)-specific mAb ACT-1 by 40%, thus de
monstrating that one integrin subfamily can regulate the activity of a
nother. To determine whether mAb 18D3 could regulate more than alpha(4
)-associated integrin-mediated costimulation, non-alpha(4) integrins w
ere tested. mAb 18D3 inhibited maximal proliferation induced by alpha(
L)-specific mAb 3D6, and an alpha(5)-specific mAb 16. This clearly dem
onstrates that a variety of integrin costimulatory molecules (of the b
eta(1), beta(2), and beta(7) subfamilies) can be regulated negatively
by mAb 18D3. To analyze the specificity of this negative regulation, o
ther cell surface costimulatory molecules were tested for susceptibili
ty to mAb 18D3. Although Abs specific for CD4, CD26, CD28, CD44, CD45R
A, or CD45RO were sufficient to activate T cells when co-immobilized w
ith anti-CDS mAb, all were refractory to the inhibitory effects of mAb
18D3. Inhibition of T cell activation directly correlated with dimini
shed IL-2 production. This suggests that mAb 18D3 selectively regulate
s integrin-dependent T cell activation by delivering a negative effect
at some common point utilized by various integrin subfamilies.