Inducible Costimulatory Molecule-B7-Related Protein 1 Interactions Are Important for the Clonal Expansion and B Cell Helper Functions of Naive, Th1, and Th2 T Cells

Smith, Karen; Brewer, James M.; Webb, P. A.; Coyle, Anthony J.; Gutierrez-Ramos, Carlos; Garside, Paul

doi:10.4049/jimmunol.170.5.2310

Cited by 64 publications

(63 citation statements)

References 33 publications

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“…In contrast, its contribution to the development of polarized helper T cell subsets has been less clear. There are conflicting reports that place ICOS solely in the differentiation of Th2 cells (5,6,54): those that suggest that it is important in Th1 cells (15,51) and studies that give ICOS a degree of significance in Th1 and Th2 cell generation (4,48,50,52). It has been unclear whether these apparently contradictory findings were simply a reflection of the individual experimental systems being used, or if ICOS was a key receptor involved in dictating polarity of Th cell responses.…”

Section: Discussionmentioning

confidence: 81%

“…This suggests that the defects noted in the type 2 response in ICOS Ϫ/Ϫ mice at day 18 postinfection may be due to the poor expansion of CD4 ϩ Th2 cells (17,48) rather than a failure to differentiate. To test this possibility, infected BALB/c and ICOS Ϫ/Ϫ mice were injected with BrdU 1 day before sacrifice, and the mLN CD4 ϩ T cells were analyzed for their ability to incorporate this thymidine analog, an indicator of proliferation, at various time points postinfection.…”

Section: Despite Initial Results Suggesting That Icos Is Required Formentioning

confidence: 94%

“…Similarly, the absence of ICOS during toxoplasmosis resulted in a reduction in the numbers of activated CD4 ϩ T cells associated with lower levels of BrdU incorporation, but those CD4 ϩ T cells that became activated were capable of producing equivalent levels of IFN-␥. Similarly, using a noninfectious model, Garside and colleagues (48) showed that, when TCR transgenic T cells specific for OVA were differentiated under Th1 or Th2 conditions in vitro and then transferred into naive recipients, both subsets required ICOS for subsequent expansion.…”

Section: Discussionmentioning

confidence: 99%

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B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses

Wilson

Zaph

Mohrs

et al. 2006

The Journal of Immunology

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Although initial reports linked the costimulatory molecule ICOS preferentially with the development of Th2 cells, there is evidence that it is not required for protective type 2 immunity to helminths and that it contributes to Th1 and Th2 responses to other parasites. To address the role of ICOS in the development of infection-induced polarized Th cells, ICOS−/− mice were infected with Trichuris muris or Toxoplasma gondii. Wild-type mice challenged with T. muris developed Th2 responses and expelled these helminths by day 18 postinfection, whereas ICOS−/− mice failed to clear worms and produced reduced levels of type 2 cytokines. However, by day 35 postinfection, ICOS−/− mice were able to mount an effective Th2 response and worms were expelled. This delay in protective immunity was associated with a defect in infection-induced increases in the number of activated and proliferating CD4+ T cells. Similarly, following challenge with T. gondii ICOS was required for optimal proliferation by CD4+ T cells. However, the reduced number of activated CD4+ T cells and associated defect in the production of IFN-γ did not result in increased susceptibility to T. gondii, but rather resulted in decreased CNS pathology during the chronic phase of this infection. Taken together, these data are consistent with a model in which ICOS is not involved in dictating polarity of the Th response but rather regulates the expansion of these subsets.

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Section: Discussionmentioning

confidence: 81%

Section: Despite Initial Results Suggesting That Icos Is Required Formentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses

Wilson

Zaph

Mohrs

et al. 2006

The Journal of Immunology

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“…The finding that ligation of ICOS without TCR stimulation can activate PI3K signaling cascades explains TCR-independent, yet PI3K-dependent ICOS function in cytoskeletal rearrangement that may have a potential role in T-cell adherence and migration (30). However, it has been shown that interruption of ICOS function does not affect T-cell trafficking itself in vivo (38,39). Regardless, it is clear that coligation of the TCR and ICOS gives rise to a maximal PI3K signaling.…”

Section: Discussionmentioning

confidence: 93%

Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase

Gigoux

Shang

Pak

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

213

258

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The T-cell costimulatory receptors, CD28 and the inducible costimulator (ICOS), are required for the generation of follicular B helper T cells (T FH) and germinal center (GC) reaction. A common signal transducer used by CD28 and ICOS is the phosphoinositide 3-kinase (PI3K). Although it is known that CD28-mediated PI3K activation is dispensable for GC reaction, the role of ICOS-driven PI3K signaling has not been defined. We show here that knock-in mice that selectively lost the ability to activate PI3K through ICOS had severe defects in T FH generation, GC reaction, antibody class switch, and antibody affinity maturation. In preactivated CD4 ؉ T cells, ICOS delivered a potent PI3K signal that was critical for the induction of the key T FH cytokines, IL-21 and IL-4. Under the same settings, CD28 was unable to activate PI3K but supported a robust secondary expansion of T cells. Thus, our results demonstrate a nonredundant function of ICOS-PI3K pathway in the generation of T FH and suggest that CD28 and ICOS play differential roles during a multistep process of T FH differentiation.CD28 ͉ follicular B helper T-cell ͉ germinal center ͉ ICOS ͉ PI3K

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“…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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Inducible Costimulatory Molecule-B7-Related Protein 1 Interactions Are Important for the Clonal Expansion and B Cell Helper Functions of Naive, Th1, and Th2 T Cells

Cited by 64 publications

References 33 publications

B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses

B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses

Inducible costimulator promotes helper T-cell differentiation through phosphoinositide 3-kinase

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

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