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. 1994 Apr;81(4):569–577.

Lytic susceptibility of target cells to cytotoxic T cells is determined by their constitutive major histocompatibility complex class I antigen expression and cytokine-induced activation status

M Ritter, C Huber, J Auböck, H Pohl-Markl, I Troppmair, M Herold, A Gächter, W Nussbaumer, G Böck, D Nachbaur, U Westhoff, B Eibl, H Schwaighofer, J Thaler, H Grosse-Wilde, D Niederwieser
PMCID: PMC1422367  PMID: 7913694

Abstract

Cytotoxic T-cell lines (TCL) were raised in vitro using stimulator cells with a defined major histocompatibility complex (MHC) mismatch and tested in a cytotoxic chromium-release assay against haemopoietic and non-haemopoietic target cells from the original stimulator. Monoclonal antibody (mAb)-blocking experiments and simultaneous determination of MHC class I, class II, lymphocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) density by quantitative radioimmunometric methods and flow cytometry on target cells demonstrated that lysis was restricted by MHC class I and dependent upon the constitutive MHC class I antigen expression. Measurements showed a high constitutive expression of class I MHC antigens on peripheral blood mononuclear cells (PBMC), but a low one on keratinocytes (K). Also, PBMC were more susceptible to lysis by TCL than K. Interferon-γ (IFN-γ) treatment of K resulted in increased MHC class I antigen expression and enhanced lytic susceptibility to TCL. IFN-α and tumour necrosis factor-α (TNF-α) treatment, which did not modulate MHC class I antigen expression on K, did not influence the amount of K lysis either. None of the cytokines tested in this analysis, however, increased the expression of MHC class I, class II, ICAM-1 and LFA-1 on PBMC. Only IFNγ pretreatment showed a minimal, statistically significant increase in MHC class I antigen expression. In spite of the minimal effect of IFN-γ and no effect of IFN-α on class I MHC expression, pretreatment of target cells with both cytokines considerably increased their lytic susceptibility. The mechanism of cytokine-induced enhanced lytic susceptibility to TCL was not explained by increased MHC class I, LFA-1 or ICAM-1 expression, since no correlation was found between surface expression of these molecules and lytic susceptibility to TCL. These data demonstrate that: (1) the constitutive density of MHC class I antigens determines the extent of TCL lysis; (2) IFN-γ, and not IFN-α or TNF-α, controls the amount of K target cell lysis by increasing their MHC class I antigen expression; and (3) IFN-γ and IFN-α control the amount of PBMC target cell lysis by a mechanism independent of MHC class I, ICAM-1 or LFA-1 expression.

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Selected References

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