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Inhibiting Treg cell function in tumors is an attractive strategy to improve anti-cancer immunity. In a pair of papers in Immunity and Cell , Ghosh and colleagues show that the canonical NF-κB subunits p65 and c-Rel have non-redundant, critical roles in promoting Treg cell development and function ( Oh et al., 2017 ). Targeting c-Rel blunts Treg cell immunosuppressive activity in the tumor microenvironment and enhances anti-tumor T cell responses ( Grinberg-Bleyer et al., 2017 ). [ABSTRACT FROM AUTHOR]

Although regulatory T cells protect people from autoimmunity, two recent papers in Immunity ( Malchow et al., 2016; Kieback et al., 2016 ) demonstrate that these cells are also a crisis averted. Without the proper education in the thymus, these cells will turn on their host and cause autoimmunity. [ABSTRACT FROM AUTHOR]

Questions regarding T cell development have recently received much attention, but the earliest intrathymic differentiation steps in adult mice have remained controversial. Three new papers together show that for at least some thymus-settling precursors, the loss of B lineage potential occurs in the thymus, and Notch acts on multipotent progenitors early after thymic entry. [Copyright &y& Elsevier]

The recent characterization of a mutant strain of mice generated five decades ago in a program to study ionizing radiation in mammals (and, ironically, derived from a nonmutagenized control animal) is helping to dissect a now resurgent area of immunology. Despite a vast literature during the 1970s, the study of suppressor T cells had been largely abandoned until the publication of several seminal papers rekindled interest in what are today generally referred to as regulatory T (TR) cells. The identification of the transcription factor Foxp3 as the gene responsible for the defect in scurfy mice, and subsequently, the demonstration of its critical involvement in the generation of TR cells, provides an important molecular insight into this essential cell lineage. [Copyright &y& Elsevier]

CD4 gene regulation provides an ideal model for understanding the molecular events that drive T cell development. In this paper we use a transgenic approach to identify a CD4 LCR containing a stage-specific thymocyte enhancer (TE) and a region that protects against position effect variegation. Surprisingly, the TE acts indirectly through the previously defined proximal enhancer and is strongly induced upon commitment to the T cell lineage. We also describe a complex series of hierarchical control element interactions that orchestrate CD4 expression throughout thymopoiesis. These data provide a framework for understanding how CD4 gene expression is regulated in response to lineage commitment decisions. [Copyright &y& Elsevier]

T follicular helper (Tfh) cells help B cells to generate affinity-matured antibodies. Three papers in this issue of Immunity () provide information about the reciprocal relationship between B cells and Tfh cells. [ABSTRACT FROM AUTHOR]

Three papers in this issue of Immunity () together reveal coordinating roles for autoreactive T cells and TNF receptor superfamily members in the development of medullary thymic epithelial cells. [Copyright &y& Elsevier]