CHARACTERIZATION OF THE HUMAN THYMIC MICROENVIRONMENT - LYMPHOEPITHELIAL INTERACTION IN NORMAL THYMUS AND THYMOMA

Recent advances in tissue culture technology and molecular biology hav e extended our understanding of the functional morphology of the thymu s. The importance of a crosstalk between lymphoid cells and stroma has been appreciated as a prerequisite for the normal development of both . The network of direct cellular interactions and soluble factors comp rising part of the microenvironment is far from being elucidated but t he highly ordered thymic architecture clearly plays a pivotal role in normal thymic function. Insight into the genetic control of stroma dev elopment is only emerging while knowledge on the genetic control of th e various steps in T cell development is already advanced and rapidly expanding. The present paper gives an overview on the cellular compone nts and matrix molecules of the human thymic microenvironment and thei r development during ontogeny. The intrathymic cytokine network is sho rtly reviewed. Special emphasis is put on molecules mediating lymphoep ithelial interactions that are necessary for the expansion and early s election of immature thymocytes from precursor cells and for the gener ation of an MHC restricted and self tolerant T cell repertoire by posi tive and negative selection. Considering these physiological mechanism s we summarize the molecular pathology of the microenvironment and lym phocyte/stroma interactions in thymic epithelial tumors (thymomas), Fi nally, a pathogenetic model for paraneoplastic myasthenia gravis is gi ven. We suggest abnormal autoantigen-specific positive selection of na ive T cells as the essential molecular mechanism by which thymomas con tribute to the autoimmunization against the acetylcholine receptor and other muscle proteins.