Uptake of membrane molecules from T cells endows antigen‐presenting cells with novel functional properties

Hoen, Esther N. M. Nolte‐‘t; Wagenaar-Hilbers, Josée P A; Peters, Peter J.; Gadella, Bart M.; Eden, Willem van; Wauben, Marca H. M.

doi:10.1002/eji.200324711

Cited by 36 publications

(42 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intercellular transfer of proteins from T cells to APCs might also balance the immune responses, as anergic or regulatory T-cell-derived vesicles have been shown to induce a tolerogenic phenotype in APCs (95). It was shown that CD8 + T cells which had acquired cognate pMHC I complexes became susceptible to antigen-specific lysis or fratricide killings, thereby contributed to effector clearance (18,23,96).…”

Section: Suppressive Effect On Immune Responsesmentioning

confidence: 99%

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

et al. 2008

View full text Add to dashboard Cite

Section: Suppressive Effect On Immune Responsesmentioning

confidence: 99%

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

et al. 2008

View full text Add to dashboard Cite

“…32 Activated T cells can also secrete bioactive EXO, [8][9][10] which can be taken up by DCs or B cells via direct intercellular molecule transfer from T cells to APCs. 11 However, the potential effect of T-cell EXO on the regulation of immune responses is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…10 In addition, T-cell EXO can be taken up by DCs or B cells by intercellular molecule transfer from T cells to antigen-presenting cells (APCs), leading to modulation of the APC and regulation of Tcell responses. 11 However, the potential effect of activated T-cell EXO on modulation of DC-induced immune responses is still largely unclear.…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cell-released exosomes inhibit CD8+ cytotoxic T-lymphocyte responses and antitumor immunity

Zhang

Xie

et al. 2010

Cell Mol Immunol

View full text Add to dashboard Cite

T cells secrete bioactive exosomes (EXO), but the potential immunoregulatory effect of T-cell EXO is largely unknown. In this study, we generated activated ovalbumin (OVA)-specific CD4 1 T cells in vitro via coculture of OVA-pulsed dendritic cells (DC OVA ) with naive CD4 1 T cells derived from OVA-specific T-cell receptor (TCR) transgenic OTII mice. CD4 1 T-cell EXO were then purified from the CD4 1 T-cell culture supernatants by differential ultracentrifugation. CD41 T-cell EXO exhibited the 'saucer' shape that is characteristic of EXO with a diameter between 50 and 100 nm, as assessed by electron microscopy, and contained the EXO-associated proteins LAMP-1, TCR and lymphocyte function associated antigen-1 (LFA-1), as determined by western blot. Flow cytometric analysis showed that CD4 1 T-cell EXO expressed CD41 T-cell markers (CD4, TCR, LFA-1, CD25 and Fas ligand), but to a lesser extent than CD4 1 T cells. We demonstrated that DC OVA took up CD4 1 T-cell EXO via peptide/major histocompatibility complex (pMHC) II/TCR and CD54/LFA-1 interactions. OVA-specific CD41 T-cell EXO from OTII mice, but not ConA-stimulated polyclonal CD4 1 T-cell EXO from wild-type C57BL/6 mice inhibited DC OVA -stimulated in vitro CD4 1 T-cell proliferation and in vivo CD8 1 cytotoxic T lymphocyte (CTL) responses and antitumor immunity against OVA-expressing B16 melanoma BL6-10 OVA cells. In addition, EXO derived from a T-cell hybridoma cell line, MF72.2D9, expressing an OVA-specific CD4 1 TCR, had a similar inhibitory effect as OTII CD4 1 T-cell EXO on CTL-mediated antitumor immunity. Taken together, our data indicate that antigen-specific T-cell EXO may serve as a new type of immunosuppressive reagent for use in transplant rejection and treatment of autoimmune diseases.

show abstract

“…It has been demonstrated that DCs can uptake T cell EXOs (15). To assess T cell EXO uptake by DCs, DC OVA were incubated with CFSE-EXO for 4 h and then analyzed by flow cytometry and confocal fluorescence microscopy.…”

Section: Uptake T Cell Exo Via Pmhc I-tcr and Cd54-lfa-1 Interactionsmentioning

confidence: 99%

“…In addition, these active T cells also secrete bioactive EXOs, which express TCRs and Fas ligand (FasL) (13,14) and can be taken up by APCs or B cells via direct cultivation (15). It has also been demonstrated that these FasLexpressing T cell EXOs induced apoptosis formation of the bystander T cells with unknown mechanism (16).…”

mentioning

confidence: 99%

Dendritic Cells Recruit T Cell Exosomes via Exosomal LFA-1 Leading to Inhibition of CD8+ CTL Responses through Downregulation of Peptide/MHC Class I and Fas Ligand-Mediated Cytotoxicity

Xie

Zhang

et al. 2010

The Journal of Immunology

106

View full text Add to dashboard Cite

Active T cells release bioactive exosomes (EXOs). However, its potential modulation in immune responses is elusive. In this study, we in vitro generated active OVA-specific CD8+ T cells by cultivation of OVA-pulsed dendritic cells (DCOVA) with naive CD8+ T cells derived from OVA-specific TCR transgenic OTI mice and purified EXOs from CD8+ T cell culture supernatant by differential ultracentrifugation. We then investigated the suppressive effect of T cell EXOs on DCOVA-mediated CD8+ CTL responses and antitumor immunity. We found that DCOVA uptake OTI T cell EXOs expressing OVA-specific TCRs and Fas ligand via peptide/MHC Ag I–TCR and CD54–LFA-1 interactions leading to downregulation of peptide/MHC Ag I expression and induction of apoptosis of DCOVA via Fas/Fas ligand pathway. We demonstrated that OVA-specific OTI T cell EXOs, but not lymphocytic choriomeningitis virus-specific TCR transgenic mouse CD8+ T cell EXOs, can inhibit DCOVA-stimulated CD8+ CTL responses and antitumor immunity against OVA-expressing B16 melanoma. In addition, these T cell EXOs can also inhibit DCOVA-mediated CD8+ CTL-induced diabetes in transgenic rat insulin promoter-mOVA mice. Interestingly, the anti–LFA-1 Ab treatment significantly reduces T cell EXO-induced inhibition of CD8+ CTL responses in both antitumor immunity and autoimmunity. EXOs released from T cell hybridoma RF3370 cells expressing OTI CD8+ TCRs have a similar inhibitory effect as T cell EXOs in DCOVA-stimulated CTL responses and antitumor immunity. Therefore, our data indicate that Ag-specific CD8+ T cells can modulate immune responses via T cell-released EXOs, and T cell EXOs may be useful for treatment of autoimmune diseases.

show abstract

Uptake of membrane molecules from T cells endows antigen‐presenting cells with novel functional properties

Cited by 36 publications

References 40 publications

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

CD4+ T cell-released exosomes inhibit CD8+ cytotoxic T-lymphocyte responses and antitumor immunity

Dendritic Cells Recruit T Cell Exosomes via Exosomal LFA-1 Leading to Inhibition of CD8+ CTL Responses through Downregulation of Peptide/MHC Class I and Fas Ligand-Mediated Cytotoxicity

Contact Info

Product

Resources

About