T-Helper Cells, Methods and Protocols. Series Methods in Molecular Biology

T helper cells are crucial components of adaptive immunity. These cells originate in the thymus, where rearrange their TCR gene loci, giving rise to a unique TCR sequence capable to recognize a specific antigen. Here they also acquire the expression of the typical surface marker CD4. Newly generated Th cells egressing from the thymus have a naïve phenotype. Indeed, these unexperienced cells are unable to undergo effector functions. Naïve cells continuously recirculate in secondary lymphoid organs, seeking for their cognate antigen expressed on class II MHC molecules on the surface of antigen-presenting cells. Once the recognition process occurs, naïve T helper cells rapidly activate and massively proliferate to generate a clonal population of cells capable to recognize the same antigen. Clonal expansion is paralleled by the acquisition of effector functions to contribute to the elimination of the invading pathogen. At least three different subsets of T helper cells have been identified in both humans and mice and are characterized by distinct effector properties to defend the organism from different types of pathogens. Th1 cells protect from intracellular bacteria and viruses, Th2 cells from parasites and helminthes, Th17 cells from extracellular bacteria and fungi. In addition to these, T follicular helper cells are specialized in promoting B cell responses. Each T helper effector program is governed by lineage-defining transcription factors that promote the expression of a typical transcriptional signature. The maturation of a naïve cell towards a specific effector phenotype occurs in the context of antigen recognition and is induced by polarizing cytokines directly released by antigen-presenting cells.