Sage Journals: Discover world-class research

Abstract

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-g, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14‡ cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GMCSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE.

Keywords

GM-CSF CD80 antigen presenting cells

Get full access to this article

View all access options for this article.

References

Lanier LL , O'Fallon S , Somoza C et al. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTI . J Immunol 1995; 154: 97–105 .

Tsokos GC , Kovacs B , Sfikakis PP , Theocharis S , Vogelgesang S . Defective antigen-presenting cell function in patients with systemic lupus erythematosus . Arthritis Rheum 1996; 39: 900–909 .

Garcia-Cozar FJ , Molina IJ , Cuadrado MJ , Marubayashi M , Pena J , Santamaria M . Defective B7 expression on antigen-presenting cells underlying T cell activation abnormalities in systemic lupus erythematosus (SLE) patients . Clin Exp Immunol 1996; 104: 72–79 .

Liu MF , Li JS , Weng TH , Lei HY . Differential expression and modulation of costimulatory molecules CD80 and CD86 on monocytes from patients with systemic lupus erythematosus . Scand J Immunol 1999; 49: 82–87 .

Zheng Z , Takahashi M , Narita M et al. Generation of dendritic cells from adherent cells of cord blood by culture with granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-a . Haematother Stem Cell Res 2000; 9: 453–464 .

Kiertscher SM , Roth MD . Human CD14 ‡ leukocytes acquire the phenotype and function of antigen-presenting dendritic cells when cultured in GM-CSF and IL-4 . J Leukocyte Biol 1996; 59: 208–218 .

Lardon F , Snoeck HW , Berneman ZN et al. Generation of dendritic cells from bone marrow progenitors using GM-CSF, TNF-a, and additional cytokines: antagonistic effects of IL-4 and IFN-g and selective involvement of TNF-a receptor-1 . Immunolgy 1997; 91: 553–559 .

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1217 .

Bombardier C , Gladman DD , Urowitz MB , Caron D , Chang CH . Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE . Arthritis Rheum 1992; 35: 630–640 .

10.

Akiyama Y , Suzuki T , Imai F , Ishibashi T , Fujimaki T . Low reactivity of peripheral blood dendritic cells respond to IL-1 and GM-CSF in SLE patients . Adv Exp Med Biol 1995; 378: 385–387 .

11.

Khwaja A , Carver J , Jones HM , Linch DC . Dynamic modulation of the cell surface expression of the granulocyte-macrophage colony-stimulating factor receptor . Br J Haematol 1993; 85: 42–49 .

12.

Walker P , Grabbe J , Zuberbier T , Grutzkau A , Henz BM . GM-CSF downmodulates c-kit, FceR1a and GM-CSF receptor expression as well as histamine and tryptase levels in cultured human nast cells . Arch Dermatol Res 2001; 293: 249–258 .

13.

Fan K , Barendsen N , Sensenbrenner L , Chen BD . Deregulation of granulocyte-macrophage colony-stimilating factor (GM-CSF) receptor in murine macrophage cell line J774A1 . J Cell Physiol 1993; 154: 535–542 .

14.

Cannistra SA , Groshek P , Garlick R , Miller J , Griffin JD . Regulation of surface expression of the granulocyte/macrophage colony-stimuloating factor receptor in normal human myeloid cells . Proc Natl Acad Sci USA 1990; 87: 93–99 .

15.

Walker F , Burgess AW . Internalisation and recycling of the granulocyte macrophage colony-stimulating factor (GM-CSF) receptor on a murine myelomonocytic leukemia . J Cell Physiol 1987; 130: 255–261 .

Dysregulation of the granulocyte-macrophage colony stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus

Abstract

Keywords

Get full access to this article

References