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

Abstract

The T-cell receptor (TCR) zeta-chain is involved in signal transduction necessary for T-cell activation and subsequent proliferation. Expression of the TCR zeta-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 zeta-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 zeta-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 zeta-chain expression. No or at most scarce expression of TCR zeta-chain was detectable in the inflammatory and neoplastic skin conditions investigated as compared to CD3-positive cells. It is possible that this TCR zeta-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 zeta-chain expression. It has been hypothesized that downregulation of the TCR zeta-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 zeta-chain expression also in inflammatory skin lymphocytic infiltrates is not consistent with a pivotal role of the TCR zeta-chain in the process of immune escape of tumour cells.