TY - JOUR
T1 - Inhibition of human T cell proliferation by CTLA-4 utilizes CD80 and requires CD25+ regulatory T cells
AU - Manzotti, Claire
AU - Tipping, Helen
AU - Perry, Laura
AU - Mead, Karen
AU - Blair, PJ
AU - Zheng, Yong
AU - Sansom, David
PY - 2002/10/1
Y1 - 2002/10/1
N2 - CD28 and CTLA-4 are opposing regulators of T cell activation, triggered by the two ligands CD80 and CD86. How these ligands promote either T cell activation via CD28 or inhibition via CTLA-4 is not understood. Using CD80 and CD86 molecules expressed on transfected cells, we have identified a major difference between these ligands in that CD80 transfectants have the ability to inhibit activation of resting human peripheral blood T cells via interaction with CTLA-4 whereas CD86 transfectants do not. Rather, CTLA-4-CD86 interactions appear to contribute towards T cell proliferation. We also observed that CTLA-4 function is strongly influenced by TCR stimulation, effects being observed only at relatively low levels of TCR stimulation. The kinetics of CD80-CTLA-4 interactions revealed that CTLA-4 inhibition took place within the first 8 h of T cell stimulation, despite there being little measurable CTLA-4 expression on the majority T cells. However, significant amounts of CTLA-4 were observed in the CD25(+) CD4(+) subset of T cells which, when removed from the cultures, accounted for the CTLA-4 inhibition observed. Overall, these data provide evidence that CD80 and CD86 differ in their interactions with CTLA-4 and that CD80 appears to be the preferential inhibitory ligand for CTLA-4 working via a population of CD4(+) CD25(+) CTLA-4(+) regulatory T cells.
AB - CD28 and CTLA-4 are opposing regulators of T cell activation, triggered by the two ligands CD80 and CD86. How these ligands promote either T cell activation via CD28 or inhibition via CTLA-4 is not understood. Using CD80 and CD86 molecules expressed on transfected cells, we have identified a major difference between these ligands in that CD80 transfectants have the ability to inhibit activation of resting human peripheral blood T cells via interaction with CTLA-4 whereas CD86 transfectants do not. Rather, CTLA-4-CD86 interactions appear to contribute towards T cell proliferation. We also observed that CTLA-4 function is strongly influenced by TCR stimulation, effects being observed only at relatively low levels of TCR stimulation. The kinetics of CD80-CTLA-4 interactions revealed that CTLA-4 inhibition took place within the first 8 h of T cell stimulation, despite there being little measurable CTLA-4 expression on the majority T cells. However, significant amounts of CTLA-4 were observed in the CD25(+) CD4(+) subset of T cells which, when removed from the cultures, accounted for the CTLA-4 inhibition observed. Overall, these data provide evidence that CD80 and CD86 differ in their interactions with CTLA-4 and that CD80 appears to be the preferential inhibitory ligand for CTLA-4 working via a population of CD4(+) CD25(+) CTLA-4(+) regulatory T cells.
KW - CD80
KW - tolerance
KW - regulatory cell
KW - CTLA-4
UR - http://www.scopus.com/inward/record.url?scp=0036773319&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(2002010)32:10<2888::AID-IMMU2888>3.0.CO;2-F
DO - 10.1002/1521-4141(2002010)32:10<2888::AID-IMMU2888>3.0.CO;2-F
M3 - Article
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
SN - 1521-4141
VL - 32
SP - 2888
EP - 2896
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 10
ER -