ICOS is essential for effective T-helper-cell responses

Tafuri, Agostino; Shahinian, Arda; Bladt, Friedhelm; Yoshinaga, Steve K.; Jordana, Manel; Wakeham, Andrew; Boucher, Louis-Martin; Bouchard, Denis; Chan, Vivien; Duncan, Gordon S.; Odermatt, Bernhard; Ho, Alexandra; Itié, Annick; Horan, Tom; Whoriskey, John; Pawson, Tony; Penninger, Josef; Ohashi, Pamela S.; Mak, Tak W.

doi:10.1038/35051113

Cited by 620 publications

(515 citation statements)

References 28 publications

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“…The IL-10-secreting phenotype was stably maintained during T cell cloning, but secretion was, to a large extent, dependent on ICOS signaling, which is in agreement with previous reports [28][29][30][31]. Of note, studies in ICOS-deficient mice have revealed a key role for this costimulatory molecule in Tdependent B cell responses [24,25]. Together, these observations suggest that the ability of ICOS to support IL-10 production by T cells plays a critical role in the provision of help to B cells.…”

Section: Discussionsupporting

confidence: 90%

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

Ebert

Horn²,

Lang³

et al. 2004

Eur J Immunol

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The CXC chemokine receptor (CXCR)5 is rapidly induced on activated CD4 + T cells, allowing migration toward secondary lymphoid tissue follicles, where the CXCR5 ligand CXCL13/ BCA-1 is produced. Such CXCR5 + T cells provide efficient help for B cell immunoglobulin production and are termed follicular B helper T (T FH ) cells. However, the molecular mechanisms by which T FH cells provide B cell help are unknown. Here, we demonstrate that newly generated (antigen-primed) T FH cells express a phenotype consistent with induction of B cell proliferation, but co-culture with primed B cells resulted in a switch to a plasma cell-inducing phenotype, characterized by loss of CD154, induction of CD70 and an increase in IL-10 production capacity. The ability to produce IL-10 could be maintained as a stable phenotype, but its secretion was strictly dependent on inducible costimulator (ICOS) signaling. Furthermore, B cells preserved a lymph node migration phenotype in proliferating T FH cells by preventing the loss of CC chemokine receptor (CCR)7 and the induction of CCR5. Thus, B cells directly modulate the B cell helper phenotype in T FH cells and actively promote their prolonged co-localization with these cells.

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Section: Discussionsupporting

confidence: 90%

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

Ebert

Horn²,

Lang³

et al. 2004

Eur J Immunol

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“…In summary, these observations demonstrate the role of a novel TNF/TNFR partner in the current models of the kinetic dynamics of human B cell stimulation and differentiation proposed by Morimoto et al [14], in addition to the other TNF/TNFR family members CD40/CD40L, CD27/CD70 and CD134/CD134L and ICOS [7,8]. Regarding the model proposed by Morimoto et al [14], LIGHT participates in the first step, i.e.…”

Section: Light Stimulation Enhances Ig Secretionsupporting

confidence: 65%

“…ICOS is expressed on both CD4 + and CD8 + activated T lymphocytes [6]. ICOS is essential for T cell-dependent B cell responses [7][8][9] and the GC reactions [10,11]. The mechanism underlying B cell activation by ICOS may, at least partially, function through the CD40/CD40L pathway [12].…”

Section: Light Stimulation Enhances Ig Secretionmentioning

confidence: 99%

LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell‐dependent B cell terminal differentiation

et al. 2004

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The T cell-dependent differentiation and function of B lymphocytes are tightly regulated by TNF ligands (L) and receptors interactions, such as CD40/CD40L, CD27/CD70 and CD134/ CD314L. The LIGHT/HVEM system [homologous to lymphotoxin, inducible expression, competing for GpD of herpes virus, that binds to the herpes virus entry mediator (HVEM), and is expressed on activated T lymphocytes) focused our attention since HVEM has a large distribution that, in addition to T cells, DC or NK, includes tumor and normal B lymphocytes. HVEM was expressed on memory and naive B cells from peripheral blood or tonsils, but not on germinal center (GC) B cells. Costimulation by CD40L+LIGHT induced LIGHT expression at the B lymphocyte surface by a transcriptional mechanism since we detected de novo expression of LIGHT-specific mRNA. LIGHTexpression was further enhanced by triggering of surface IgM, a stimulus that mimics a normal step of B cell physiology, i.e. specific antigen encounter. Stimulation by LIGHT increased the B cell proliferation induced by CD40L, and induced IgG and IgM (but not IgA) secretion. We conclude that LIGHT costimulation, that mimics the B cell encounter with activated LIGHT-expressing T lymphocytes, enhances both B cell proliferation and Ig production, and thus has a central importance for humoral immunity development.

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“…Of the costimulatory molecules we assessed, ICOS was the one most strongly up-regulated on activated CXCR5 + CD8 T cells. In mice, a lack of ICOS results in severely deficient T cell-dependent B cell responses with impaired GC formation and Ig class switching [41]. Thus, ICOS fulfills a non-redundant function in the interaction between T and B cells.…”

Section: Discussionmentioning

confidence: 99%

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

et al. 2007

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Naive and central memory CD8 T cells use CCR7 to recirculate through T cell zones of secondary lymphoid organs where they can encounter antigen. Here we describe a subset of human CD8 T cells expressing CXCR5 which enables homing in response to CXCL13 produced within B cell follicles. CXCR5 + CD8 T cells were found in tonsil B cell follicles, and isolated cells migrated towards CXCL13 in vitro. They expressed CD27, CD28, CD45RO, CD69, and were CD7 low , and produced IFN-c and granzyme A but lacked perforin, a functional profile suggesting that these cells are early effector memory cells in the context of contemporary T cell differentiation models. Receptors important in the interaction with B cells, including CD70, OX40 and ICOS, were induced upon activation, and CXCR5 + CD8 T cells could to some extent support survival and IgG production in tonsil B cells. Furthermore, CXCR5 + CD8 T cells expressed CCR5 but no CCR7, suggesting a migration pattern distinct from that of follicular CD4 T cells. The finding that a subset of early effector memory CD8 T cells use CXCR5 to locate to B cell follicles indicates that MHC class I-restricted CD8 T cells are part of the follicular T cell population. IntroductionCD8 T cells are lymphocytes of the adaptive immune system which recognize viral and bacterial peptides presented by MHC class I molecules and are indispensable in the control of many intracellular infections [1]. When appropriately stimulated by antigen presented by dendritic cells (DC) in secondary lymphoid tissues, they proliferate vigorously, become effector cells, and upon resolution of infection a small population of antigen-specific CD8 T cells are maintained as long-lived memory cells [2][3][4]. A primary effector mechanism of CD8 T cells is the killing of infected cells via the targeted release of the lytic effector molecules perforin and granzymes, and via expression of death receptors. However, there is significant functional heterogeneity in CD8 T cells and they are also efficient in producing anti-viral and pro-inflammatory cytokines [5][6][7][8]. The effector mechanisms used may depend on the pathogen and on the type of cell or tissue that is infected [8].CD8 T cell responses involve the differentiation of naive T cells into distinct types of effector and memory cells [2, 3,9]. One approach to analyse a T cell response is to examine the expression of receptors that mediate homing of T cells, such as CD62L, which binds to glycosylation-dependent cell adhesion molecule 1 on [4,20,21]. CXCR5 is a chemokine receptor which is expressed on all B cells and on specialized subsets of DC and T cells [22]. It has only one known ligand, the chemokine CXCL13, mainly produced by stromal cells and follicular DC within B cell follicles [23][24][25]. CXCR5 + CD4 T cells, known as follicular homing T helper cells, are found in B cell follicles and contribute to the generation of effective humoral immune responses by supporting antibody production and isotype class switching [26,27]. However, some of the processes and mec...

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ICOS is essential for effective T-helper-cell responses

Cited by 620 publications

References 28 publications

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell‐dependent B cell terminal differentiation

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

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ICOS is essential for effective T-helper-cell responses

Cited by 620 publications

References 28 publications

B cells alter the phenotype and function of follicular‐homing CXCR5+ T cells

B cells alter the phenotype and function of follicular‐homing CXCR5+ T cells

LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell‐dependent B cell terminal differentiation

CXCR5+ CCR7– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles

Contact Info

Product

Resources

About

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

CXCR5⁺ CCR7^– CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles