Single Naive CD4+ T Cells from a Diverse Repertoire Produce Different Effector Cell Types during Infection

Tubo, Noah J.; Pagán, Antonio J.; Taylor, Justin J.; Nelson, Ryan; Linehan, Jonathan L.; Ertelt, James M.; Huseby, Eric S.; Way, Sing Sing; Jenkins, Marc K.

doi:10.1016/j.cell.2013.04.007

Cited by 405 publications

(549 citation statements)

References 58 publications

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“…The G‐protein‐coupled receptor EBI‐2 positions T cells in this location, where Tfh cell differentiation is further enhanced by DC‐mediated production of soluble and membrane‐bound CD25 (the IL‐2 receptor α chain), which binds to and quenches IL‐2 128. Signals received via the TCR during DC‐mediated antigen presentation also influence CD4 + differentiation into early Tfh cells, although there is not a simple relationship between TCR signal strength and Tfh cell differentiation 129. Instead, the duration of signaling appears more important, with Tfh cell induction being associated with prolonged antigen presentation by DC 130…”

Section: T Follicular Helper Cells and Their Role In Bnab Inductionmentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

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Moody

2017

Immunological Reviews

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SummaryInduction of broadly neutralizing antibodies (bnAbs) capable of inhibiting infection with diverse variants of human immunodeficiency virus type 1 (HIV‐1) is a key, as‐yet‐unachieved goal of prophylactic HIV‐1 vaccine strategies. However, some HIV‐infected individuals develop bnAbs after approximately 2‐4 years of infection, enabling analysis of features of these antibodies and the immunological environment that enables their induction. Distinct subsets of CD4+ T cells play opposing roles in the regulation of humoral responses: T follicular helper (Tfh) cells support germinal center formation and provide help for affinity maturation and the development of memory B cells and plasma cells, while regulatory CD4+ (Treg) cells including T follicular regulatory (Tfr) cells inhibit the germinal center reaction to limit autoantibody production. BnAbs exhibit high somatic mutation frequencies, long third heavy‐chain complementarity determining regions, and/or autoreactivity, suggesting that bnAb generation is likely to be highly dependent on the activity of CD4+ Tfh cells, and may be constrained by host tolerance controls. This review discusses what is known about the immunological environment during HIV‐1 infection, in particular alterations in CD4+ Tfh, Treg, and Tfr populations and autoantibody generation, and how this is related to bnAb development, and considers the implications for HIV‐1 vaccine design.

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Section: T Follicular Helper Cells and Their Role In Bnab Inductionmentioning

confidence: 99%

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

Borrow

Moody

2017

Immunological Reviews

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“…The use of terms such as lineage, specification and master regulator are terms best aligned with developmental programmes, such as in Caenorhabditis elegans, in which the fate of each cell is predetermined and irreversible. Nature Reviews | Immunology T H 2 or T FH cell differentiation can dominate [55][56][57][58] . By contrast, weak TCR signalling, by transient or low-affinity TCR interactions, favours the induction of FOXP3 expression 59,60 .…”

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confidence: 99%

Harnessing the plasticity of CD4+ T cells to treat immune-mediated disease

2016

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| CD4 + T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4 + T cell plasticity by examining the molecular mechanisms that regulate it -from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.

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“…In a recent chapter of this continuing story, the sensitivity of the tetramer-based cell-enrichment method brought us back to the adoptive-transfer approach to study the naive to effector cell transition but this time by transferring single naive CD4 1 T cells (44). I never dreamed as I was measuring swollen mouse ears and culturing T cells in 96-well plates that someday my colleagues would be tracking the fates of single epitope-specific T cells during an immune response.…”

mentioning

confidence: 99%