Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells

J Immunol. 1994 Jun 1;152(11):5208-19.


Dendritic cells (DC) play a critical role in the initiation of T cell-mediated immune responses, and express costimulatory molecules that are required for optimal activation of unprimed T cells. Studies on the regulation of the costimulatory molecules on DC have produced evidence from several systems that GM-CSF can up-regulate expression of CTLA4 counter receptor (CTLA4-CR) (but not intercellular adhesion molecule 1 (ICAM-1) and heat stable Ag (HsAg)) on DC. This is demonstrated on splenic DC, Langerhans cells, kidney DC in culture, and in a skin-explant culture system, in which the increased expression of CTLA4-CR on Langerhans cells (LC) occurs concomitantly with their migration out of skin. Interestingly, despite the ability of both GM-CSF and IFN-gamma to increase CTLA4-CR and maintain similar levels of ICAM-1, HsAg, and MHC molecule expression, the functional consequences of these cytokines on splenic DC are distinctly different. GM-CSF enhances the ability of DC to stimulate both T cell proliferation and cytokine release, whereas IFN-gamma causes no increase in immunostimulatory function. Further analysis of the CTLA4-CR on these cell populations by using the GL-1 and IG10 mAbs has shown that GM-CSF-cultured DC express high levels of both B7-1 and B7-2, whereas IFN-gamma-cultured DC express increased levels of only B7-2. These results suggest that optimal stimulation of unprimed T cells to proliferate and release cytokines may require participation of both of these CTLA4 counter receptors, and confirm the importance of GM-CSF for the maturation of DC into potent stimulators of T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD*
  • Antigens, Differentiation / physiology
  • B7-1 Antigen / analysis*
  • B7-2 Antigen
  • Base Sequence
  • CTLA-4 Antigen
  • Cell Line
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Immunoconjugates*
  • Interferon-gamma / pharmacology
  • Langerhans Cells / physiology
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Molecular Sequence Data


  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CTLA-4 Antigen
  • Cd86 protein, mouse
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Membrane Glycoproteins
  • Abatacept
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor