TY - JOUR
T1 - Modulatory effect of aggregating the CD3 molecular complex on T cell activation
AU - Gur, H.
AU - Wacholtz, M. C.
AU - Davis, L. S.
AU - Geppert, T. D.
AU - Lipsky, P. E.
PY - 1992/3
Y1 - 1992/3
N2 - The role of cross-linking the TCR CD3 complex in the induction of T cell activation was examined using human peripheral blood T cells and the Jurkat leukemic T cell line. IL-2 production was induced from these cells by pulsing them with mAb to CD3 and costimulating with phorbol myristate acetate (PMA). Cross-linking the anti-CD3 mAb with soluble goat anti-mouse immunoglobulin (GaMIg) markedly inhibited IL-2 production by these cells. Soluble GaMIg did not induce a generalized inhibition of IL-2 production as it was required for responses induced by mAb to class I MHC molecules. In addition, cross-linking anti-CD3 mAb with GaMIg did not inhibit IL-2 production induced by PMA and ionomycin. Inhibition of IL-2 production induced by soluble GaMIg reflected diminished accumulation of mRNA for IL-2. By contrast, immobilized GaMIg was a potent stimulus for IL-2 production by T cells pulsed with anti-CD3 mAb and costimulated with PMA. Cross-linking anti-CD3 with soluble GaMIg induced enhanced aggregation of the ligated molecules, but it did not alter the profile of the change in intracellular calcium induced. To determine whether cross-linking of mAb played a role in inducing IL-2 production as well as in limiting responsiveness, F(ab) fragments were employed. F(ab) fragments of anti-CD3 mAb failed to induce IL-2 production by PMA costimulated Jurkat cells. However, cross-linking of anti-CD3 F(ab)-pulsed Jurkat cells with low concentrations of soluble GaMIg induced IL-2 production in the presence of PMA, whereas higher concentrations suppressed responses. The data indicate that induction of IL-2 production requires aggregation of the TCR CD3 complex, whereas excessive cross-linking diminishes the induction of IL-2 production. Moreover, the results indicate that various biologic activities of the CD3 molecular complex, including aggregation, signaling capability, and the ability to induce IL-2 gene transcription, are differentially affected by cross-linking.
AB - The role of cross-linking the TCR CD3 complex in the induction of T cell activation was examined using human peripheral blood T cells and the Jurkat leukemic T cell line. IL-2 production was induced from these cells by pulsing them with mAb to CD3 and costimulating with phorbol myristate acetate (PMA). Cross-linking the anti-CD3 mAb with soluble goat anti-mouse immunoglobulin (GaMIg) markedly inhibited IL-2 production by these cells. Soluble GaMIg did not induce a generalized inhibition of IL-2 production as it was required for responses induced by mAb to class I MHC molecules. In addition, cross-linking anti-CD3 mAb with GaMIg did not inhibit IL-2 production induced by PMA and ionomycin. Inhibition of IL-2 production induced by soluble GaMIg reflected diminished accumulation of mRNA for IL-2. By contrast, immobilized GaMIg was a potent stimulus for IL-2 production by T cells pulsed with anti-CD3 mAb and costimulated with PMA. Cross-linking anti-CD3 with soluble GaMIg induced enhanced aggregation of the ligated molecules, but it did not alter the profile of the change in intracellular calcium induced. To determine whether cross-linking of mAb played a role in inducing IL-2 production as well as in limiting responsiveness, F(ab) fragments were employed. F(ab) fragments of anti-CD3 mAb failed to induce IL-2 production by PMA costimulated Jurkat cells. However, cross-linking of anti-CD3 F(ab)-pulsed Jurkat cells with low concentrations of soluble GaMIg induced IL-2 production in the presence of PMA, whereas higher concentrations suppressed responses. The data indicate that induction of IL-2 production requires aggregation of the TCR CD3 complex, whereas excessive cross-linking diminishes the induction of IL-2 production. Moreover, the results indicate that various biologic activities of the CD3 molecular complex, including aggregation, signaling capability, and the ability to induce IL-2 gene transcription, are differentially affected by cross-linking.
UR - http://www.scopus.com/inward/record.url?scp=0026513688&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026513688&partnerID=8YFLogxK
U2 - 10.1016/0008-8749(92)90178-R
DO - 10.1016/0008-8749(92)90178-R
M3 - Article
C2 - 1531456
AN - SCOPUS:0026513688
VL - 140
SP - 81
EP - 96
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 1
ER -