Modulation of expression of class II histocompatibility antigens by secretion of a cellular inhibitor in K562 leukemic cells

Abstract

In this report we show that it is possible to induce the expression of HLA-DR antigens on K562 cells, previously reported to be unresponsive to interferon-gamma (IFN-gamma). However, only low cell concentrations and a high dose of IFN-gamma allowed the induction of HLA-DR antigens. Furthermore, the recombinant glycosylated IFN-gamma is 100-fold more efficient than the unglycosylated form. This induction of HLA-DR antigens on K562 was not related to a stage of differentiation or to the presence of cells subsets specifically sensitive to IFN-gamma, since repeated sorting of K562 HLA-DR-positive and negative cells did not lead to the selection of a cell subset with a different potential of induction for HLA-DR. The difficulty in obtaining induction is due to the production of a soluble endogenous inhibitor of proteic nature, whose action is not restricted to the K562 cell line since it operates also on both epithelial and fibroblastic cells. Treatment of normal human epithelial and fibroblastic cells with conditioned medium from K562 cultures caused a marked decrease in the expression of HLA class II antigens (DR and DP) induced by IFN-gamma (10,000 U/ml), but had no effect on cell growth; however, it also affected expression of HLA class I antigens. This inhibition is not mediated by prostaglandin or an IFN-alpha or IFN-beta-dependent mechanism. Production of this inhibitor by pluripotent human leukemic cells could cause an unbalance in the complex control exerted by the immunological system during hematopoietic differentiation or leukemic progression.

Inhibitor (IK) of IFN-γ induced HLA class II antigens expression also inhibits HLA class II constitutive expression in the human Raji B cell line

“…Zhou and Glimcher (1995) have suggested that the CIITA protein should be one of the determinant factors involved in the MHC class II transcriptional <ON/ OFF> switch. In our laboratory we have characterised a new protein IK which inhibits the IFN-g induced MHC class II expression (Krief et al, 1987(Krief et al, , 1994. In this paper we discuss the role of this new molecule in the regulation of constitutive MHC class II expression.…”

“…This ®nding provides a new element in similarity between constitutive and inducible MHC class II regulation pathways. In the case of several cell lines, we have demonstrated that the induction of MHC class II surface expression could only be obtained in conditions of high IFN-g concentration and low cellular density (Krief et al, 1987). These observations have led us to characterise and to purify a new protein called IK (Inhibitor K562), originally described as a speci®c secreted inhibitor of IFN-g induced MHC class II antigen expression (Krief et al, 1994).…”

IK Induced by Coxsackievirus B3 Infection Transiently Downregulates Expression of MHC Class II Through Increasing cAMP

“…It has been reported that IK is an efficient inhibitor of IFNc-induced MHC class II expression and it was originally isolated from the conditioned culture medium of the K562 erythroleukemic cell line (25). IK has also been implicated in the inhibition of constitutive MHC class II expression through the repression of class II transactivator (CIITA) (33,49), a factor that regulates MHC class II expression (10,43).…”

Infection of a human leukemia K-562 cell line with Semliki Forest virus

“…[1][2][3], susceptibility to natural killer (NK) cell activity [4] which varies markedly in sublines with distinctive karyotypes [5], continuous or environmentally modulated expression of a variety of hematopoietic cell differentiation antigens [6,7], and the secretion of cell growth inhibitory factors [8,9]. These cells do not normally express HLA class I or class II antigens but class I antigens are expressed in Burkitt-K-562 hybrids [ 10-1, and can be induced in K-562 cells with Interleukin 1 [11], sodium butyrate or moderate levels of human interferons [7,12].…”

“…These cells do not normally express HLA class I or class II antigens but class I antigens are expressed in Burkitt-K-562 hybrids [ 10-1, and can be induced in K-562 cells with Interleukin 1 [11], sodium butyrate or moderate levels of human interferons [7,12]. High levels of interferons can induce the expression of HLA-DR, a class II antigen, which is normally not expressed by these cells because they secrete an inhibitory factor(s) [9]. In addition, the specific chromosomal translocation (i.e., Ph 1) results in the creation of a chimeric oncogene, bcr/abl, [13,14] which is amplified 4-to 8-fold [15], and gene product P210, which is an active tyrosine kinase [15,16] that appears to be growth stimulatory [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]17].…”