ICOS is critical for CD40-mediated antibody class switching

McAdam, Alexander J.; Greenwald, Rebecca J.; Levin, Michele; Chernova, Tatyana; Malenkovich, Nelly; Ling, Vincent; Freeman, Gordon J.; Sharpe, Arlene H.

doi:10.1038/35051107

Cited by 596 publications

(479 citation statements)

References 22 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: 91%

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: 91%

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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“…ICOS has been considered an inducible T-cell costimulatory molecule important for CD40-mediated Ab class switching [30]; however, the recent studies of uncontrolled expression of ICOS in several gene-modified mice showing lupus-like pathology provide insight for the close relationship between ICOS-expressing CD4 1 T cells and autoimmunity [19,31]. In the present study, blockade of ICOS using neutralizing Ab significantly reduced the production of total IgG in RASV-administered MyD88 À/À mice, suggesting possible cross-talk between Tfh-like cells and B cells via ICOS-ICOSL interaction for hyper-IgG.…”

Section: Discussionmentioning

confidence: 99%

Expansion of Tfh‐like cells during chronic Salmonella exposure mediates the generation of autoimmune hypergammaglobulinemia in MyD88‐deficient mice

Yang

et al. 2011

Eur J Immunol

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The role of TLR signaling in linking the innate and adaptive immune systems has been a controversial issue that remains to be solved. Here, we determined whether MyD88-dependent TLR signals are required for the generation of B-cell responses during chronic Salmonella infection. Oral administration of recombinant attenuated Salmonella enterica serovar Typhimurium vaccine (RASV) strain in MyD88 À/À mice resulted in chronic infection. Infection was accompanied by enlarged germinal centers and hypergammaglobulinemia with anti-double-stranded DNA (dsDNA)-specific Ab in sera, and the deposition of immune complexes in the kidneys, suggesting onset of autoimmunity. CD4 1 T cells expressing PD-1, CXCR5, ICOS, and IL-21 were dramatically increased in chronically infected mice, indicating the expansion of follicular helper T (Tfh)-like cells. Of note, the depletion of CD4 1 T cells completely blocked the generation of polyclonal IgG Ab in sera after oral RASV challenge. Inflammatory myeloid cells expressing CD11b and Gr-1 accumulated in high numbers in the spleen of MyD88 À/À mice. Interestingly, the blockade of PD-1 or ICOS significantly reduced the hypergammaglobulinemia and dsDNA-specific autoantibody production. Overall, these results suggest that Tfh-like cells in chronic bacterial infection trigger autoimmune hypergammaglobulinemia in a PD-1-and ICOSdependent manner.

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“…However, the interactions between the different pathways and their interdependence on each other are only now becoming clear. This is especially true for the ICOS-B7RP1, B7-CD28/CTLA4 and CD40-CD154 pathways (26,27,34). For example, T-cell ICOS up-regulation is reduced in the absence of B7.1 and B7.2, but is restored following CD28 stimulation (26), whereas CTLA4 ligation blocks ICOS costimulation by preventing cell-surface expression and downstream second signals (27).…”

Section: Discussionmentioning

confidence: 99%

Interaction Between ICOS-B7RP1 and B7-CD28 Costimulatory Pathways in Alloimmune Responses In Vivo

Salama

Yuan

Nayer

et al. 2003

American Journal of Transplantation

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The B7-CD28 pathway is one of the foremost costimulatory pathways involved in T-cell activation. Recently, a number of additional costimulatory pathways have been described and preliminary data suggest that they play important roles in alloimmunity. However, the interactions between these different pathways are not well understood. We studied the effect of targeting ICOS ligand, B7RP1, in a rat cardiac transplant model, with and without concomitant blockade of the B7 pathway using CTLA4Ig. In a fully mismatched WF to LEW vascularized cardiac allograft model, without therapy, grafts were acutely rejected (MST 10.8 -1.6 days). Early (day of transplant) B7RP1 blockade with ICOSIg alone had little effect on graft survival and rather than being additive with B7 blockade, ICOSIg abrogated the prolonged graft survival induced by CTLA4Ig treatment. By contrast, delayed (day 2 posttransplant) blockade of B7RP1 did not have such an effect. These findings were not related to cytokine deviation but may be in part related to the pattern of down-regulation of B7.2 expression following early B7RP1 blockade. This is the first report describing the complex interactions between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmunity in vivo.

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ICOS is critical for CD40-mediated antibody class switching

Cited by 596 publications

References 22 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

Expansion of Tfh‐like cells during chronic Salmonella exposure mediates the generation of autoimmune hypergammaglobulinemia in MyD88‐deficient mice

Interaction Between ICOS-B7RP1 and B7-CD28 Costimulatory Pathways in Alloimmune Responses In Vivo

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ICOS is critical for CD40-mediated antibody class switching

Cited by 596 publications

References 22 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

Expansion of Tfh‐like cells during chronic Salmonella exposure mediates the generation of autoimmune hypergammaglobulinemia in MyD88‐deficient mice

Interaction Between ICOS-B7RP1 and B7-CD28 Costimulatory Pathways in Alloimmune Responses In Vivo

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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