Synergy between CD28 and CD9 costimulation for naive T-cell activation

Toyo-oka, Kazuhito; Tai, Xuguang; Yashiro, Yumi; Ahn, Hyun-Jong; Ryo, Akihide; Hamaoka, Toshiyuki; Kobayashi, Michiko; Neben, Steven; Fujiwara, Hiromi

doi:10.1016/s0165-2478(97)02706-5

Cited by 12 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8) as well as CD5, CD9 and CD44 (data not shown). Our previous study showed that CD9 co-stimulation, when com- bined with CD28 co-stimulation, induced a synergy in T cell activation [25]. Consistent with this, the combination of CD2 or CD5 co-stimulation as examples of non-CD28 co-stimulation with CD28 co-stimulation resulted in a synergy in contrast to the additive effect again observed for the coupled co-stimulation of CD2 and CD5 (Exp.…”

Section: The Combined Co-stimulation Of Non-cd28 Molecules Induces Onsupporting

confidence: 67%

A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other co-stimulatory molecules

et al. 1998

Self Cite

View full text Add to dashboard Cite

T cell activation requires two signals: a signal from the TCR and a co-stimulatory signal provided by antigen-presenting cells (APC). In addition to CD28, multiple molecules on the T cell have been described to deliver co-stimulatory signals. Here, we investigated whether there exist quantitative or qualitative differences in the co-stimulatory capacity between CD28 and other molecules. Anti-CD28 monoclonal antibody (mAb) and mAb against CD5, CD9, CD2, CD44 or CD11a all induced activation of naive T cells in the absence of APC when co-immobilized with a submitogenic dose of anti-CD3 mAb. [3H]Thymidine incorporation determined 2 days after co-stimulation was all comparable. In contrast to progressive T cell proliferation induced by CD28 co-stimulation, co-stimulation by other T cell molecules led to a decrease in viable cell recovery along with the induction of apoptosis of once activated T cells. This was associated with a striking difference in IL-2 production; CD28 co-stimulation induced progressively increasing IL-2 production, whereas co-stimulation by other molecules produced limited amounts of IL-2. Addition of recombinant IL-2 to the latter cultures corrected the induction of apoptosis, resulting in levels of cellular proliferation comparable to those observed for CD28 co-stimulation. These results indicate that a fundamental difference exists in the nature of co-stimulation between CD28 and other molecules, which can be evaluated by the levels of IL-2 production, but not simply by [3H]thymidine incorporation.

show abstract

Section: The Combined Co-stimulation Of Non-cd28 Molecules Induces Onsupporting

confidence: 67%

A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other co-stimulatory molecules

et al. 1998

Self Cite

View full text Add to dashboard Cite

show abstract

“…A costimulatory effect of CD9 ligation on murine naive lymph node T cells was also reported [92]. It was found to be independent of CD28 and to operate synergistically with this molecule [93]. Interestingly, in contrast to CD28 costimulation, initial activation induced by the CD9 mAb is followed by apoptosis, which can be prevented by addition of IL-2 [94].…”

Section: Costimulation and Signal Transductionmentioning

confidence: 92%

Tetraspanins

Boucheix¹,

Rubinstein²

2001

CMLS, Cell. Mol. Life Sci.

578

629

View full text Add to dashboard Cite

The first tetraspanins were discovered on surface of human leucocytes, but it was rapidly demonstrated that they had a wider tissue expression. Twenty-six molecules display sufficient homology to belong to the same superfamily. Their function is not precisely known, but data coming from biochemical studies or knockout mice suggest that they play a major role in membrane biology. One of their outstanding properties is their ability to form a network of multimolecular complexes, the 'tetraspanin web', in which integrins are included. The structure of these complexes is under investigation, but some of the rules that govern their organization have already been unraveled. The challenge is to determine how the organization of the 'tetraspanin web' modifies the function of its constitutive molecules and consequently influences cellular behaviour. The implications may be considerable for the understanding of basic cellular processes such as migration and also of diseases related to loss or mutation of a single tetraspanin.

show abstract

“…Indeed, classical markers for early and late T cell activation (CD69, TACTILE, LAG3, or SLAM), expression of cytotoxicity-associated genes such as granzyme, perforin, fas, and granulysin (28), and genes characterizing proinflammatory Th1/Th2 responses (TNF␣, IL-4, and IL-10) were consistently reduced in TOL patients. Approximately 90% of known proinflammatory cytokines were reduced in TOL patients, supporting evidence for immune quiescence and ignorance of donor antigen (29,30). Interestingly, a modest enrichment (P ϭ 0.025) for genes identified in memory T cells (31) was seen in the expression signature from our TOL patients.…”

Section: Altered Immunological Circuits In Operational Tolerancementioning

confidence: 94%

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance

Brouard

Mansfield

Braud

et al. 2007

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

336

312

View full text Add to dashboard Cite

Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous ''operational tolerance'' with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients in which IS could be tapered and hinders the development of new tolerance-inducing strategies. The objective of this study was to identify minimally invasive blood biomarkers for operational tolerance and use these biomarkers to determine the frequency of this state in immunosuppressed patients with stable graft function. Blood gene expression profiles from 75 renal-transplant patient cohorts (operational tolerance/acute and chronic rejection/stable graft function on IS) and 16 healthy individuals were analyzed. A subset of samples was used for microarray analysis where three-class comparison of the different groups of patients identified a ''tolerant footprint'' of 49 genes. These biomarkers were applied for prediction of operational tolerance by microarray and real-time PCR in independent test groups. Thirty-three of 49 genes correctly segregated tolerance and chronic rejection phenotypes with 99% and 86% specificity. The signature is shared with 1 of 12 and 5 of 10 stable patients on triple IS and low-dose steroid monotherapy, respectively. The gene signature suggests a pattern of reduced costimulatory signaling, immune quiescence, apoptosis, and memory T cell responses. This study identifies in the blood of kidney recipients a set of genes associated with operational tolerance that may have utility as a minimally invasive monitoring tool for guiding IS titration. Further validation of this tool for safe IS minimization in prospective clinical trials is warranted.kidney transplantation ͉ microarray ͉ tolerant ͉ genomics ͉ immunosuppression titration D espite continuous improvement in renal allograft survival over the last decade, the half-life of renal allografts has increased marginally because of accrual of chronic graft nephropathy from drug-related nephrotoxicity and chronic rejection (1, 2). Patients facing life-long immunosuppression (IS) have increased risk of infection and malignancy (3), whereas insufficient immunosuppressive drug exposure or interruption usually increases rejection risk (4). However, spontaneous and long-term graft acceptance is observed in a small number of patients after solid-organ transplantation (5, 6), years after total withdrawal of immunosuppressive drugs, confirming that a clinical operational state of tolerance to a mismatched graft, described as ''a state of quiescence of the transplanted organ, functioning without a destructive immune response'' (7), can indeed occur and exist in humans. However, the frequency of this observation in the kidney transplant population is unknown and, currently, we cannot identify patients primed to develop this immune adaptation or monitor for the stability of this status of ''operational tolerance.'' The operationally tolerant kidney transpla...

show abstract

Synergy between CD28 and CD9 costimulation for naive T-cell activation

Cited by 12 publications

References 30 publications

A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other co-stimulatory molecules

A fundamental difference in the capacity to induce proliferation of naive T cells between CD28 and other co-stimulatory molecules

Tetraspanins

Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance

Contact Info

Product

Resources

About