Regulation of CD28 expression on CD8+ T cells by CTLA-4

Berg, Martina; Zavazava, Nicholas

doi:10.1189/jlb.0107065

Cited by 23 publications

(21 citation statements)

References 58 publications

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“…Consistent with earlier reports (12, 19 -21), we observed that Ag presentation in the presence of blocking Ab against CD86, but not CD80, resulted in significantly lower effector T cell proliferation than in controls. In addition, whereas selective costimulation by CD86 ϩ T cells results in down-regulation of CD28 expression on the surface upon activation (22). However, our observation that CD4 ϩ T cells costimulated preferentially by either CD80 or CD86, or both had comparable levels of CD28 and CTLA-4 on their surface (not shown).…”

Section: Discussioncontrasting

confidence: 52%

Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-β1+-Adaptive Regulatory T Cell Generation

Pérez¹,

Karumuthil‐Melethil²,

Li³

et al. 2008

The Journal of Immunology

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Costimulatory ligands CD80 and CD86 have different binding preferences and affinities to their receptors, CD28 and CTLA-4. Earlier, we demonstrated that CD80 binds to CTLA-4 with higher affinity and has a role in suppressing T cell response. The current study demonstrates that not only did blockade of CD86 upon Ag presentation by bone marrow-derived dendritic cells (DC) to OVA-specific T cells result in induction of hyporesponsive T cells but also that these T cells could suppress the proliferative response of effector T cells. These T cells showed TGF-β1 on their surface and secreted TGF-β1 and IL-10 upon restimulation. Although blockade of CTLA-4 and neutralization of IL-10 profoundly inhibited the induction of these TGF-β1+ T cells, their ability to suppress the effector T cell proliferation was abrogated by neutralization of TGF-β1 alone. Induction of TGF-β1+ and IL-10+ T cells was found to be independent of natural CD4+CD25+ regulatory T cells, demonstrating that preferential ligation of CTLA-4 by CD80 induced IL-10 production by effector T cells, which in turn promoted the secretion of TGF-β1. Treatment of prediabetic NOD mice with islet β cell Ag-pulsed CD86−/− DCs, but not CD80−/− DCs, resulted in the induction of TGF-β1- and IL-10-producing cells, significant suppression of insulitis, and delay of the onset of hyperglycemia. These observations demonstrate not only that CD80 preferentially binds to CTLA-4 but also that interaction during Ag presentation can result in IL-10-dependent TGF-β1+ regulatory T cell induction, reinstating the potential of approaches to preferentially engage CTLA-4 through CD80 during self-Ag presentation in suppressing autoimmunity.

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Section: Discussioncontrasting

confidence: 52%

Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-β1+-Adaptive Regulatory T Cell Generation

Pérez¹,

Karumuthil‐Melethil²,

Li³

et al. 2008

The Journal of Immunology

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“…Observed CD28 downregulation in the ENU group indicates depressed immune status and poor T-cell activation and is evidenced in human cancers in other studies [17] but such downregulation in glioma and its reconstituted expression is being shown here for the first time. CD28 downregulation results from increased CTLA-4 expression [38]. This supports present observations where CTLA-4 expression was elevated in glioma conditions.…”

Section: Discussionsupporting

confidence: 82%

“…T11TS causes CD28 and CD80 upregulation and CTLA-4 downregulation. CD28 upregulation and CTLA-4 blockade leads to immuno-enhancement and abolishes glioma-induced immunesuppression [38,40]. Observed CTLA-4 suppression by T11TS therapy may aid alleviation of glioma-induced immunesuppression and since CTLA-4 suppression is concurrent to CD28 upregulation, such alleviation in immune responses and of T-cell proliferation may occur through activation of the PI3K-Akt pathways to which the CD28-mediated costimulation is linked [41].…”

Section: Discussionmentioning

confidence: 95%

“…IL-10 upregulation suppresses CD3 [49], MHC-II [50,51] and CD28 [52], and TGF-b upregulation leads to downregulated MHC-II and CD80 and to CTLA-4 upregulation [50,53]. IFN-c upregulation causes upregulation of CD3f [49]; MHC-II [54] and CD80 [38]; reduced IFN-c causes reduced CD2 expression [51]. Enhanced TNF-a production results in MHC-II [54] and CD80 [55] upregulations.…”

Section: Discussionmentioning

confidence: 99%

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The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation

Chaudhuri

Singh²,

Bhattacharya³

et al. 2014

J Neurooncol

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T-cell-mediated immune responses are typically low in conditions of malignant glioma which has been known to cause marked immunesuppression and dysregulate major T-cell signaling molecules. Thus, T-cell-based immunotherapies are currently in vogue in the treatment of malignant glioma. The novel glycopeptide, T11TS/S-LFA-3/S-CD58 has previously been shown by our group to be highly efficacious in glioma abrogation in in vivo and in vitro conditions. This glycopeptide ligands to the costimulatory CD2 molecule on T-cells, causing profound immune stimulation leading to glioma abrogation, suggesting probable involvement of T11TS in modulation of the T-cell signaling pathway. The present study offers a multi-targeted approach towards repair of some of the key components of the immunological synapse at the T-cell-APC interface and is therefore the first of its kind to offer a holistic model of restoration of immunological synapse components so as to trigger T-cells towards activation against glioma. The study thus indicates that the totally dysregulated molecular events at the immunological synapse in glioma are restored back to normal levels with the administration of T11TS, which finally culminates in glioma abrogation. The present study thus delineates an important T-cell signaling approach whereby T11TS acts as an anti-neoplastic agent, thus helping to chart out newer avenues in the fight against gliomas.

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“…We did not measured CTLA-4 (cytotoxic T lymphocyte antigen-4), the homologous family member of CD28. CTLA-4 and CD28 take opposing effect in the activation and differention of T helper cells [40,41] and it is theoretically possible that antagonistic effects may have been induced without our knowledge (though we think this unlikely). Therefore, clinical trials are required to assess whether our observation translates into clinical outcomes related to survival or the immune response.…”

Section: Discussionmentioning

confidence: 97%

Differential effects of propofol and isoflurane on the activation of T‐helper cells in lung cancer patients

Ren

Meng

et al. 2010

Anaesthesia

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SummaryIt is suggested that activation and differentiation of T-helper cells are required for peri-operative anti-tumor and anti-infection immunity. The present study aimed to evaluate whether propofol stimulates the activation and differentiation of these cells in patients undergoing pulmonary lobectomy for non-small-cell lung cancer. Thirty patients were randomly allocated to receive propofol or isoflurane throughout surgery. The CD4 + CD28 + percentage (p < 0.0001) and the ratio of interferon-c:interleukin-4 (p = 0.001) all increased with propofol but showed no change with isoflurane. In contrast, cortisol increased with isoflurane (p < 0.0001) but not with propofol over time (p = 0.06). We conclude that propofol promotes activation and differentiation of peripheral T-helper cells.

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Regulation of CD28 expression on CD8+ T cells by CTLA-4

Cited by 23 publications

References 58 publications

Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-β1+-Adaptive Regulatory T Cell Generation

Preferential Costimulation by CD80 Results in IL-10-Dependent TGF-β1+-Adaptive Regulatory T Cell Generation

The novel immunotherapeutic molecule T11TS modulates glioma-induced changes of key components of the immunological synapse in favor of T cell activation and glioma abrogation

Differential effects of propofol and isoflurane on the activation of T‐helper cells in lung cancer patients

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