Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function

Schaerli, Patrick; Willimann, Katharina; Lang, Aloïs B.; Lipp, Martin; Loetscher, Pius; Moser, Bernhard

doi:10.1084/jem.192.11.1553

Cited by 1,100 publications

(1,016 citation statements)

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“…found that the number of antigen‐specific memory cells that expressed Tfh markers declined over time, suggesting that Tfh cells fail to differentiate into long‐lived memory cells 57. However, we and others have shown that both mouse and human CXCR5+ memory CD4 T‐cells provide rapid assistance to B‐cells upon reactivation 61, 62, 63, 64, 65, 66, 67, 68, 69. Importantly, Alexander et al .…”

Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 74%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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SummaryImmunological memory provides rapid protection to pathogens previously encountered through infection or vaccination. CD4 T‐cells play a central role in all adaptive immune responses. Vaccines must, therefore, activate CD4 T‐cells if they are to generate protective immunity. For many diseases, we do not have effective vaccines. These include human immunodeficiency virus (HIV), tuberculosis and malaria, which are responsible for many millions of deaths each year across the globe. CD4 T‐cells play many different roles during the immune response coordinating the actions of many other cells. In order to harness the diverse protective effects of memory CD4 T‐cells, we need to understand how memory CD4 T‐cells are generated and how they protect the host. Here we review recent findings on the location of different subsets of memory CD4 T‐cells that are found in peripheral tissues (tissue resident memory T‐cells) and in the circulation (central and effector memory T‐cells). We discuss the generation of these cells, and the evidence that demonstrates how they provide immune protection in animal and human challenge models.

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Section: Memory Cd4 T‐cells Are Found Throughout the Bodymentioning

confidence: 74%

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

2018

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“…As CD4 + T cells differentiate into pre‐Tfh cells they downregulate expression of C‐C chemokine receptor type 7 (CCR7) and P‐selectin glycoprotein ligand 1 (PSGL‐1), which promote localization to and retention within the T‐cell zone, and upregulate expression of the chemokine receptor characteristic of Tfh cells, C‐X‐C chemokine receptor type 5 (CXCR5), which binds C‐X‐C motif chemokine ligand 13 (CXCL13), a chemokine produced in B‐cell follicles 131, 132. This enables pre‐Tfh cells to migrate to the margin of the B‐cell follicle,133 where they interact with B cells and the next step in Tfh differentiation takes place.…”

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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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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“…The differentiation of these long‐lived B cells is linked to the differentiation of follicular T helper (Tfh) cells, a subset of CD4 + T cells that is specialized in providing help to B cells in the germinal center (GC) reaction (Breitfeld et al , 2000; Schaerli et al , 2000). …”

Section: Introductionmentioning

confidence: 99%

The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

et al. 2016

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Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long‐term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4+ T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell‐intrinsic manner. Our data indicate that T cell‐expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell‐dependent B‐cell responses.

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Cxc Chemokine Receptor 5 Expression Defines Follicular Homing T Cells with B Cell Helper Function

Cited by 1,100 publications

References 50 publications

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

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

The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6

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