Adult human glial cells can present target antigens to HLA-restricted cytotoxic T-cells

Abstract

T-lymphocyte recognition of antigen either on antigen-presenting cells (APC) necessary for the generation of an immune response or on target cells during the effector phase of a cellular immune response requires expression of HLA molecules. Although immune mechanisms operate in many disease processes of the central nervous system (CNS), cells of the CNS generally express low levels of HLA molecules. In this study, the potential for upregulation of HLA molecules on adult human glial cells was examined. Moreover, the functional implication of this upregulation was assessed by the capacity of glial cells to process and present target antigens to HLA class I-restricted influenza-specific and class II-restricted myelin basic protein (MBP)-specific CTL lines. Glial cells cultured from adult human surgical brain specimens or cells from established glioblastoma multiforme cell lines were studied. Lysis by antigen-specific CTLs was dependent on treatment of the target cell with interferon-gamma. The lysis was HLA restricted and antigen specific. The results indicate that adult human glial cells can process and present antigen to HLA-restricted CTLs but require the upregulation of HLA molecules. These findings have implications for infectious and autoimmune diseases of the CNS.

Malignant glioma cells use MHC class II transactivator (CIITA) promoters III and IV to direct IFN‐γ‐inducible CIITA expression and can function as nonprofessional antigen presenting cells in endocytic processing and CD4+ T‐cell activation

“…Neoplastic cells and some infiltrating mononuclear cells within MGs express MHC class I and class II molecules (Rossi et al, 1987;Saito et al, 1988;Tran et al, 1998), suggesting that these cells may be capable of Ag presentation to CD8 ϩ and CD4 ϩ TIL, respectively. In this regard, it has been observed that MG tumor cells can present Ag to class I-restricted cytolytic CD8 ϩ T cells (Dhib-Jalbut et al, 1990) and, although MG tumor Ags have not been well characterized (Chi et al, 1997), data suggest that expansion of CD8 ϩ TIL in MGs is Ag driven (Perrin et al, 1999). In contrast, deficiencies in T-cell activation have been observed in CD4 ϩ T cells isolated from MG tumor tissue and peripheral blood of affected individuals (Roszman et al, 1991).…”

All in the head: obstacles for immune rejection of brain tumours

“…It is thus essential that MHC molecules are induced either during tumorigenesis or during immunotherapy‐induced anti‐tumour responses if classical CTL‐mediated cytotoxicity is to be operational. For tumour cells of astrocytic origin, these uniformly express MHC class I molecules after in vitro culture, and can be induced to express MHC class II after interferon‐γ (IFN‐γ) treatment (refs 46, 56–58 and our own unpublished observations). The situation in vivo is far from clear, with contradictory reports in the literature 54,55 , 59,60 .…”

“…The generally low MHC expression by normal tissue may actually be an advantage during immunotherapy in that it may spare normal tissue from immune attack. However, normal astrocytes show inducible MHC expression, particularly after incubation with IFN‐γ in vitro 56,61–65 . In vivo , as for neoplastic cells, the situation is more complicated.…”

“…However, normal astrocytes show inducible MHC expression, particularly after incubation with IFN-c in vitro. 56,[61][62][63][64][65] In vivo, as for neoplastic cells, the situation is more complicated. Based on data from mouse models, some studies have demonstrated that astrocytes can be induced to express MHC class I molecules after viral infection or exposure to IFN-c. [66][67][68] However, other authors have suggested that in the absence of degenerated neurones, the oligodendrocyte and the microglial cell are the principal MHC-expressing cells of the non-malignant brain.…”

Interleukin-1β decreases HLA class II expression on a glioblastoma multiforme cell line

“…For example, following treatment with interferon-T (IFN-T), astrocytes, endothelial cells, and microglia can all be induced to express MHC molecules in vitro (Dhib-Jalbut and Mc-Farlin, 1989). In addition, when induced to express MHC molecules, astrocytes and endothelial cells have been shown to present antigen to T cells McCarron et al, 1985;Sun and Wekerle, 1986;Dhib-Jalbut et al, 1990).…”