Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion

Morita, Rimpei; Schmitt, Nathalie; Bentebibel, Salah Eddine; Ranganathan, Rajaram; Bourdery, Laure; Zurawski, Gérard; Foucat, Emile; Dullaers, Mélissa; Oh, Sang Kon; Sabzghabaei, Natalie; Lavecchio, Elizabeth M.; Punaro, Marilynn; Pascual, Virginia; Banchereau, Jacques; Ueno, Hideki

doi:10.1016/j.immuni.2010.12.012

Cited by 1,298 publications

(1,435 citation statements)

References 62 publications

Supporting

Mentioning

1,354

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…T‐cell‐mediated ligation of CD40 on the B cell triggers B‐cell clonal expansion and differentiation,96 and cytokines produced by the T cell including interleukin (IL)‐21 and IL‐4 promote growth and differentiation and direct Ig class switching 97, 98. Provision of help is dependent on an active two‐way interaction between the B and T cell, with inducible T‐cell costimulatory (ICOS) triggering being important for IL‐21 production99 and IL‐4 production being dependent on signaling lymphocytic activation molecule (SLAM) 100. Following activation, the B cells may differentiate into short‐lived extrafollicular plasma cells that have very few mutations in their Ig variable (V)‐region genes and secrete low‐affinity Ig, develop into early memory B cells, or undergo proliferation within the follicle, giving rise to GCs (reviewed in 101).…”

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

confidence: 99%

“…They are found within the CXCR5 + subset of circulating CD4 + T cells,99, 159 although CXCR5 + can also be expressed on non‐Tfh cells. Precise definition of circulating memory Tfh cells is challenging, as resting memory Tfh cells in blood do not express Bcl6 or the high levels of PD‐1 and ICOS characteristic of GC Tfh cells and require re‐stimulation in order to mediate B‐cell helper activity 99, 159, 160, 162. A subpopulation of blood CXCR5 + CD4 + T cells expresses PD‐1, although at lower levels than GC Tfh cells.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…As expression of the CXCR5 chemokine receptor on CD4 ϩ T cells ostensibly defines a subset of pTfh cells in peripheral blood (7,19,21), we assessed whether specific gp120-specific B cell memory subsets were associated with CXCR5 ϩ CD4 ϩ T cells. Overall, gp120-specific RM and IM cells were significantly expanded in HIV EC (P ϭ 0.0004 and P ϭ 0.04, respectively), while the AM cell subset was larger in HIV progressors (P ϭ 0.01), as was the TLM subset, albeit to a lower degree ( Fig.…”

Section: Bulk B Cells Are Expanded In Uncontrolled Hiv Infection Butmentioning

confidence: 99%

“…To further explore functional impairment in pTfh cells in HIV progressors compared to controllers, we next performed coculture assays to directly determine whether CD4 helper quality varies between PBMCs derived from these two cohorts in response to both global and antigen-specific stimulation, as previously shown (21,22). Specimens from both HIV VC and HIV EC were grouped for this analysis to achieve sufficient statistical power.…”

Section: Bulk B Cells Are Expanded In Uncontrolled Hiv Infection Butmentioning

confidence: 99%

Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers

Buranapraditkun

Pissani

Teigler

et al. 2017

J Virol

View full text Add to dashboard Cite

The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the factors associated with perturbation of the B cell compartment seem to be favorable for the generation of highly affinity-matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, the impact of HIV antigenemia on B cells and Tfh cell interactions warrants further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120 probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5 ϩ CD4 ϩ T cells were significantly diminished in HIV progressors, we found that a small subset of gp120-specific interleukin-21 (IL-21)-secreting CXCR5 ϩ CD4 ϩ T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5 ϩ CD4 ϩ T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting memory subset, whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, CXCR5 ϩ CD4 ϩ T cells from elite controllers showed a stronger ex vivo capacity to induce B cell maturation and immunoglobulin class switching than cells from HIV progressors.IMPORTANCE Dissecting the factors that are involved in B cell maturation and antibody development is important for HIV vaccine design. In this study, we found that HIV Env-specific CXCR5 ϩ CD4 ϩ T cells that secrete interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than those of HIV progressors.

show abstract

Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion

Cited by 1,298 publications

References 62 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

Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers

Contact Info

Product

Resources

About