Eintrag weiter verarbeiten
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients
Gespeichert in:
| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , , |
| In: | The Journal of Immunology, 194, 2015, 8, S. 3768-3777 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
|
| Schlagwörter: |
| author_facet |
Kaltenmeier, Christof Gawanbacht, Ali Beyer, Thamara Lindner, Stefanie Trzaska, Timo van der Merwe, Johannes Andreas Härter, Georg Grüner, Beate Fabricius, Dorit Lotfi, Ramin Schwarz, Klaus Schütz, Catharina Hönig, Manfred Schulz, Ansgar Kern, Peter Bommer, Martin Schrezenmeier, Hubert Kirchhoff, Frank Jahrsdörfer, Bernd Kaltenmeier, Christof Gawanbacht, Ali Beyer, Thamara Lindner, Stefanie Trzaska, Timo van der Merwe, Johannes Andreas Härter, Georg Grüner, Beate Fabricius, Dorit Lotfi, Ramin Schwarz, Klaus Schütz, Catharina Hönig, Manfred Schulz, Ansgar Kern, Peter Bommer, Martin Schrezenmeier, Hubert Kirchhoff, Frank Jahrsdörfer, Bernd |
|---|---|
| author |
Kaltenmeier, Christof Gawanbacht, Ali Beyer, Thamara Lindner, Stefanie Trzaska, Timo van der Merwe, Johannes Andreas Härter, Georg Grüner, Beate Fabricius, Dorit Lotfi, Ramin Schwarz, Klaus Schütz, Catharina Hönig, Manfred Schulz, Ansgar Kern, Peter Bommer, Martin Schrezenmeier, Hubert Kirchhoff, Frank Jahrsdörfer, Bernd |
| spellingShingle |
Kaltenmeier, Christof Gawanbacht, Ali Beyer, Thamara Lindner, Stefanie Trzaska, Timo van der Merwe, Johannes Andreas Härter, Georg Grüner, Beate Fabricius, Dorit Lotfi, Ramin Schwarz, Klaus Schütz, Catharina Hönig, Manfred Schulz, Ansgar Kern, Peter Bommer, Martin Schrezenmeier, Hubert Kirchhoff, Frank Jahrsdörfer, Bernd The Journal of Immunology CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients Immunology Immunology and Allergy |
| author_sort |
kaltenmeier, christof |
| spelling |
Kaltenmeier, Christof Gawanbacht, Ali Beyer, Thamara Lindner, Stefanie Trzaska, Timo van der Merwe, Johannes Andreas Härter, Georg Grüner, Beate Fabricius, Dorit Lotfi, Ramin Schwarz, Klaus Schütz, Catharina Hönig, Manfred Schulz, Ansgar Kern, Peter Bommer, Martin Schrezenmeier, Hubert Kirchhoff, Frank Jahrsdörfer, Bernd 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.1402568 <jats:title>Abstract</jats:title> <jats:p>IL-21 can induce both plasma cells and regulatory B cells. In this article, we demonstrate that untreated HIV patients display CD4+ T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B. Granzyme B–expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10. The main functional characteristic of their regulatory activity is direct granzyme B–dependent degradation of the TCR-ζ–chain, resulting in significantly decreased proliferative T cell responses. Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L. When culturing such IL-21+CD40L− Th cells with B cells, the former directly induce B cell differentiation into GraB cells. In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21–dependent B cell differentiation. As proof of principle, we confirmed this mechanism in a patient lacking intact CD40 signaling due to a NEMO mutation. The majority of peripheral B cells from this patient were GraB cells and strongly suppressed T cell proliferation. In conclusion, GraB cells represent potent regulatory B cells in humans that are phenotypically and functionally distinct from B10 cells and occur in early HIV infection. GraB cells may contribute significantly to immune dysfunction in HIV patients, and may also explain ineffective Ab responses after vaccination. The use of soluble CD40L multimers may help to improve vaccination responses in HIV patients.</jats:p> CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients The Journal of Immunology |
| doi_str_mv |
10.4049/jimmunol.1402568 |
| facet_avail |
Online Free |
| finc_class_facet |
Medizin |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuNDA0OS9qaW1tdW5vbC4xNDAyNTY4 |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuNDA0OS9qaW1tdW5vbC4xNDAyNTY4 |
| institution |
DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 |
| imprint |
The American Association of Immunologists, 2015 |
| imprint_str_mv |
The American Association of Immunologists, 2015 |
| issn |
0022-1767 1550-6606 |
| issn_str_mv |
0022-1767 1550-6606 |
| language |
English |
| mega_collection |
The American Association of Immunologists (CrossRef) |
| match_str |
kaltenmeier2015cd4tcellderivedil21anddeprivationofcd40signalingfavortheinvivodevelopmentofgranzymebexpressingregulatorybcellsinhivpatients |
| publishDateSort |
2015 |
| publisher |
The American Association of Immunologists |
| recordtype |
ai |
| record_format |
ai |
| series |
The Journal of Immunology |
| source_id |
49 |
| title |
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_unstemmed |
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_full |
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_fullStr |
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_full_unstemmed |
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_short |
CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_sort |
cd4+ t cell–derived il-21 and deprivation of cd40 signaling favor the in vivo development of granzyme b–expressing regulatory b cells in hiv patients |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.1402568 |
| publishDate |
2015 |
| physical |
3768-3777 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>IL-21 can induce both plasma cells and regulatory B cells. In this article, we demonstrate that untreated HIV patients display CD4+ T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B. Granzyme B–expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10. The main functional characteristic of their regulatory activity is direct granzyme B–dependent degradation of the TCR-ζ–chain, resulting in significantly decreased proliferative T cell responses. Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L. When culturing such IL-21+CD40L− Th cells with B cells, the former directly induce B cell differentiation into GraB cells. In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21–dependent B cell differentiation. As proof of principle, we confirmed this mechanism in a patient lacking intact CD40 signaling due to a NEMO mutation. The majority of peripheral B cells from this patient were GraB cells and strongly suppressed T cell proliferation. In conclusion, GraB cells represent potent regulatory B cells in humans that are phenotypically and functionally distinct from B10 cells and occur in early HIV infection. GraB cells may contribute significantly to immune dysfunction in HIV patients, and may also explain ineffective Ab responses after vaccination. The use of soluble CD40L multimers may help to improve vaccination responses in HIV patients.</jats:p> |
| container_issue |
8 |
| container_start_page |
3768 |
| container_title |
The Journal of Immunology |
| container_volume |
194 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792341947490238466 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:26:24.738Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=CD4%2B+T+Cell%E2%80%93Derived+IL-21+and+Deprivation+of+CD40+Signaling+Favor+the+In+Vivo+Development+of+Granzyme+B%E2%80%93Expressing+Regulatory+B+Cells+in+HIV+Patients&rft.date=2015-04-15&genre=article&issn=1550-6606&volume=194&issue=8&spage=3768&epage=3777&pages=3768-3777&jtitle=The+Journal+of+Immunology&atitle=CD4%2B+T+Cell%E2%80%93Derived+IL-21+and+Deprivation+of+CD40+Signaling+Favor+the+In+Vivo+Development+of+Granzyme+B%E2%80%93Expressing+Regulatory+B+Cells+in+HIV+Patients&aulast=Jahrsd%C3%B6rfer&aufirst=Bernd&rft_id=info%3Adoi%2F10.4049%2Fjimmunol.1402568&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792341947490238466 |
| author | Kaltenmeier, Christof, Gawanbacht, Ali, Beyer, Thamara, Lindner, Stefanie, Trzaska, Timo, van der Merwe, Johannes Andreas, Härter, Georg, Grüner, Beate, Fabricius, Dorit, Lotfi, Ramin, Schwarz, Klaus, Schütz, Catharina, Hönig, Manfred, Schulz, Ansgar, Kern, Peter, Bommer, Martin, Schrezenmeier, Hubert, Kirchhoff, Frank, Jahrsdörfer, Bernd |
| author_facet | Kaltenmeier, Christof, Gawanbacht, Ali, Beyer, Thamara, Lindner, Stefanie, Trzaska, Timo, van der Merwe, Johannes Andreas, Härter, Georg, Grüner, Beate, Fabricius, Dorit, Lotfi, Ramin, Schwarz, Klaus, Schütz, Catharina, Hönig, Manfred, Schulz, Ansgar, Kern, Peter, Bommer, Martin, Schrezenmeier, Hubert, Kirchhoff, Frank, Jahrsdörfer, Bernd, Kaltenmeier, Christof, Gawanbacht, Ali, Beyer, Thamara, Lindner, Stefanie, Trzaska, Timo, van der Merwe, Johannes Andreas, Härter, Georg, Grüner, Beate, Fabricius, Dorit, Lotfi, Ramin, Schwarz, Klaus, Schütz, Catharina, Hönig, Manfred, Schulz, Ansgar, Kern, Peter, Bommer, Martin, Schrezenmeier, Hubert, Kirchhoff, Frank, Jahrsdörfer, Bernd |
| author_sort | kaltenmeier, christof |
| container_issue | 8 |
| container_start_page | 3768 |
| container_title | The Journal of Immunology |
| container_volume | 194 |
| description | <jats:title>Abstract</jats:title> <jats:p>IL-21 can induce both plasma cells and regulatory B cells. In this article, we demonstrate that untreated HIV patients display CD4+ T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B. Granzyme B–expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10. The main functional characteristic of their regulatory activity is direct granzyme B–dependent degradation of the TCR-ζ–chain, resulting in significantly decreased proliferative T cell responses. Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L. When culturing such IL-21+CD40L− Th cells with B cells, the former directly induce B cell differentiation into GraB cells. In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21–dependent B cell differentiation. As proof of principle, we confirmed this mechanism in a patient lacking intact CD40 signaling due to a NEMO mutation. The majority of peripheral B cells from this patient were GraB cells and strongly suppressed T cell proliferation. In conclusion, GraB cells represent potent regulatory B cells in humans that are phenotypically and functionally distinct from B10 cells and occur in early HIV infection. GraB cells may contribute significantly to immune dysfunction in HIV patients, and may also explain ineffective Ab responses after vaccination. The use of soluble CD40L multimers may help to improve vaccination responses in HIV patients.</jats:p> |
| doi_str_mv | 10.4049/jimmunol.1402568 |
| facet_avail | Online, Free |
| finc_class_facet | Medizin |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuNDA0OS9qaW1tdW5vbC4xNDAyNTY4 |
| imprint | The American Association of Immunologists, 2015 |
| imprint_str_mv | The American Association of Immunologists, 2015 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
| issn | 0022-1767, 1550-6606 |
| issn_str_mv | 0022-1767, 1550-6606 |
| language | English |
| last_indexed | 2024-03-01T16:26:24.738Z |
| match_str | kaltenmeier2015cd4tcellderivedil21anddeprivationofcd40signalingfavortheinvivodevelopmentofgranzymebexpressingregulatorybcellsinhivpatients |
| mega_collection | The American Association of Immunologists (CrossRef) |
| physical | 3768-3777 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| publisher | The American Association of Immunologists |
| record_format | ai |
| recordtype | ai |
| series | The Journal of Immunology |
| source_id | 49 |
| spelling | Kaltenmeier, Christof Gawanbacht, Ali Beyer, Thamara Lindner, Stefanie Trzaska, Timo van der Merwe, Johannes Andreas Härter, Georg Grüner, Beate Fabricius, Dorit Lotfi, Ramin Schwarz, Klaus Schütz, Catharina Hönig, Manfred Schulz, Ansgar Kern, Peter Bommer, Martin Schrezenmeier, Hubert Kirchhoff, Frank Jahrsdörfer, Bernd 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.1402568 <jats:title>Abstract</jats:title> <jats:p>IL-21 can induce both plasma cells and regulatory B cells. In this article, we demonstrate that untreated HIV patients display CD4+ T cells with enhanced IL-21 expression and high in vivo frequencies of regulatory B cells overexpressing the serine protease granzyme B. Granzyme B–expressing regulatory B cells (GraB cells) cells from HIV patients exhibit increased expression of CD5, CD43, CD86, and CD147 but do not produce IL-10. The main functional characteristic of their regulatory activity is direct granzyme B–dependent degradation of the TCR-ζ–chain, resulting in significantly decreased proliferative T cell responses. Although Th cells from HIV patients secrete IL-21 in a Nef-dependent manner, they barely express CD40L. When culturing such IL-21+CD40L− Th cells with B cells, the former directly induce B cell differentiation into GraB cells. In contrast, the addition of soluble CD40L multimers to T cell/B cell cultures redirects B cell differentiation toward plasma cells, indicating that CD40L determines the direction of IL-21–dependent B cell differentiation. As proof of principle, we confirmed this mechanism in a patient lacking intact CD40 signaling due to a NEMO mutation. The majority of peripheral B cells from this patient were GraB cells and strongly suppressed T cell proliferation. In conclusion, GraB cells represent potent regulatory B cells in humans that are phenotypically and functionally distinct from B10 cells and occur in early HIV infection. GraB cells may contribute significantly to immune dysfunction in HIV patients, and may also explain ineffective Ab responses after vaccination. The use of soluble CD40L multimers may help to improve vaccination responses in HIV patients.</jats:p> CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients The Journal of Immunology |
| spellingShingle | Kaltenmeier, Christof, Gawanbacht, Ali, Beyer, Thamara, Lindner, Stefanie, Trzaska, Timo, van der Merwe, Johannes Andreas, Härter, Georg, Grüner, Beate, Fabricius, Dorit, Lotfi, Ramin, Schwarz, Klaus, Schütz, Catharina, Hönig, Manfred, Schulz, Ansgar, Kern, Peter, Bommer, Martin, Schrezenmeier, Hubert, Kirchhoff, Frank, Jahrsdörfer, Bernd, The Journal of Immunology, CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients, Immunology, Immunology and Allergy |
| title | CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_full | CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_fullStr | CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_full_unstemmed | CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_short | CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| title_sort | cd4+ t cell–derived il-21 and deprivation of cd40 signaling favor the in vivo development of granzyme b–expressing regulatory b cells in hiv patients |
| title_unstemmed | CD4+ T Cell–Derived IL-21 and Deprivation of CD40 Signaling Favor the In Vivo Development of Granzyme B–Expressing Regulatory B Cells in HIV Patients |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.1402568 |