The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

MARIA CECILIA RODRIGUEZ-GALAN ; JULIANA DE MEIS ; ANA ROSA PEREZ ; WILSON SAVINO

New insights into thymic functions during stress, aging and in disease settings

Frontiers Media SA

Lugar: Laussanne; Año: 2020; p. 1 - 228

New Insights Into Thymic Functions During Stress, Aging, and in Disease SettingsThe thymus is a bi-lobed lymphoid organ localized above the heart whose primary function isto foster the development of the T cells of the adaptive immune system. T cells are a criticalcomponent of the cellular immune system, helping B cells produce antibodies, releasing cytokinesto orchestrate effective immune responses, and killing infected cells and/or neoplasm/tumor cells.The recognition of an infected cell or tumor cell, and the ability to support B cell secretion ofantibodies requires T cells express a cell surface receptor, termed the T cell receptor (TCR). Thisreceptor selectively binds to peptides complexed to major histocompatibility complex antigens(MHC class I and II). MHC class I molecules are present on all nucleated cells in the body, whileMHC class II is restricted to antigen presenting cells. In the thymus, thymocytes rearrange DNAloci comprising the genes encoding the TCR subunits. Using a process termed VDJ recombination,each thymocyte expresses a unique TCR with exclusive recognition specificities. However, onlythose thymocytes expressing TCRs that can engage self-peptides/self MHC complexes present onthymic epithelial cells (TECs) are ?selected? to form the peripheral T cell repertoire. This involvesprocesses coined positive and negative selection, with the ensuing repertoire of T cells capableof recognizing pathogen- or distinct tumor- derived peptides presented on self-MHC moleculeswithout overt reactivity to self-peptides. The critical role of the thymus in this process is bestexemplified with infants born with mutations in genes required for the formation of the thymus(22q11.2 deletion syndrome or DiGeorge). No thymus results in no T cells, leading to a severecombined immunodeficiency. A second excellent example pertains to the spontaneously arisingnude mouse, which lacks a thymus and hair due to mutations in the Forkhead Box N1 transcriptionfactor. This transcription factor supports the development of TECs, the controllers of T cell fate,and defective TECs means no T cells (continue...)