Absent or low expression of T-cell receptor ζ-chain in T cells infiltrating human pathological skin conditions

Abstract.

The T-cell receptor (TCR) ζ-chain is involved in signal transduction necessary for T-cell activation and subsequent proliferation. Expression of the TCR ζ-chain in vivo has been studied by a variety of technical approaches on different cell and tissue specimen. However, the in situ situation concerning the expression of the TCR ζ-chain has not yet been investigated on infiltrating T lymphocytes in neoplastic and inflammatory cutaneous diseases. In this study, we analysed the expression of the TCR ζ-chain in a number of skin tissues affected by established inflammatory and neoplastic conditions. Serial sections of different tissue specimens were stained immunoenzymatically for CD3 and TCR ζ-chain expression. No or at most scarce expression of TCR ζ-chain was detectable in the inflammatory and neoplastic skin conditions investigated as compared to CD3-positive cells. It is possible that this TCR ζ-chain deletion is induced by the skin microenvironment as an effect of local immunoregulatory influences. Alternatively, lymphocytes located in the skin may generally not express this molecule. In our study, tumour-infiltrating T lymphocytes of CTCL were negative for TCR ζ-chain expression. It has been hypothesized that downregulation of the TCR ζ-chain on tumour-infiltrating T lymphocytes is a mechanism by which neoplastic cells escape the cellular immune response. Our findings showing the absence or reduction of TCR ζ-chain expression also in inflammatory skin lymphocytic infiltrates is not consistent with a pivotal role of the TCR ζ-chain in the process of immune escape of tumour cells.