Inhibition of human T cell proliferation by CTLA-4 utilizes CD80 and requires CD25+ regulatory T cells

Eur J Immunol. 2002 Oct;32(10):2888-96. doi: 10.1002/1521-4141(2002010)32:10<2888::AID-IMMU2888>3.0.CO;2-F.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD / physiology
  • Antigens, Differentiation / physiology*
  • B7-1 Antigen / physiology*
  • B7-2 Antigen
  • CD28 Antigens / physiology
  • CHO Cells
  • CTLA-4 Antigen
  • Cricetinae
  • Humans
  • Immune Tolerance
  • Immunoconjugates*
  • Lymphocyte Activation*
  • Membrane Glycoproteins / physiology
  • Receptors, Interleukin-2 / physiology*
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoconjugates
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • Abatacept