ICOS Ligand Costimulation Is Required for T-Cell Encephalitogenicity

Sporici, Romeo A.; Beswick, Richard L.; Allmen, Carolyn von; Rumbley, Catherine A.; Hayden-Ledbetter, Martha; Ledbetter, Jeffrey A.; Perrin, Peter J.

doi:10.1006/clim.2001.5074

Cited by 69 publications

(56 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relative role of ICOS in regulating IFN-c and IL-10 production is not clear, but these results are consistent with previous reports, which demonstrated that ICOS blockade was associated with decreased IFN-c and IL-10 production in several disease models such as acute allograft rejection, collageninduced arthritis, and EAE [18,34,35]. On the other hand, the production of IL-10, but not IFN-c, was comparable between the presence of anti-B7RP-1 and control IgG when added to in vitro restimulation.…”

Section: Discussionsupporting

confidence: 89%

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

et al. 2006

View full text Add to dashboard Cite

ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4 + T cells in the region of the retina in EAU-induced mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN-c production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS-mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU.

show abstract

Section: Discussionsupporting

confidence: 89%

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Novel strategies, including the use of reagents that are known to synergize with costimulatory blockade in prolonging allograft survival (for example, rapamycin and 15-deoxyspergualin) (24,41,55,56), are attractive, but their specific effect on memory T cells needs to be evaluated in detail. Finally, recent studies have provided evidence that certain newly recognized costimulatory pathways, such as ICOS/B7RP-1 and OX40/OX40L (CD134/CD134L), may be involved in reactivation of memory T cells, but have little effect on naive T cells (57)(58)(59)(60)(61). Targeting these novel pathways (in combination with CD40/CD40L blockade) is a promising, although still unproven approach for inhibiting alloreactive memory CD4 ϩ T cell function in vivo.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Helper Functions of Alloreactive Memory CD4+ T Cells Remain Intact Despite Donor-Specific Transfusion and Anti-CD40 Ligand Therapy

Chen¹,

Heeger

Valujskikh³

2004

The Journal of Immunology

125

137

View full text Add to dashboard Cite

Memory T cells have specific properties that are beneficial for rapid and efficient protection from pathogens previously encountered by a host. These same features of memory T cells may be deleterious in the context of a transplanted organ. Consistent with this contention is the accumulating evidence in experimental transplantation that previously sensitized animals are resistant to the effects of costimulatory blockade. Using a model of murine cardiac transplantation, we now demonstrate that alloreactive memory CD4+ T cells prevent long-term allograft survival induced through donor-specific cell transfusion in combination with anti-CD40 ligand Ab (DST/anti-CD40L). We show that memory donor-reactive CD4+ T cells responding through the direct or indirect pathways of allorecognition provide help for the induction of antidonor CD8+ T effector cells and for Ab isotype switching, despite DST/anti-CD40L. The induced pathogenic antidonor immunity functions in multiple ways to subsequently mediate graft destruction. Our findings show that the varied functions of alloreactive memory CD4+ T cells remain intact despite DST/anti-CD40L-based costimulatory blockade, a finding that will likely have important implications for designing approaches to induce tolerance in human transplant recipients.

show abstract

“…The ICOS-B7RP1 pathway has been shown to play a role in both alloimmune and autoimmune responses (10)(11)(12)(13)(14)(15)(16). In fully MHC-mismatched murine and rat allotransplantation models, its inhibition results in a modest prolongation of cardiac and liver allograft survival (10,13).…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

ICOS Ligand Costimulation Is Required for T-Cell Encephalitogenicity

Cited by 69 publications

References 30 publications

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

In Vivo Helper Functions of Alloreactive Memory CD4+ T Cells Remain Intact Despite Donor-Specific Transfusion and Anti-CD40 Ligand Therapy

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

Contact Info

Product

Resources

About