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26 results on '"Souwer, Yuri"'

5. Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifies HLA-DOA mRNA as a prognostic factor for survival

Author

Souwer, Yuri, Chamuleau, Martine E. D., van de Loosdrecht, Arjan A., Tolosa, Eva, Jorritsma, Tineke, Muris, Jettie J. F., Dinnissen-van Poppel, Marion J., Snel, Sander N., van de Corput, Lisette, Ossenkoppele, Gert J., Meijer, Chris J. L. M., Neefjes, Jacques J., and Marieke van Ham, S.

Published
2009
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8. The Nature of Antibacterial Adaptive Immune Responses against Staphylococcus aureus Is Dependent on the Growth Phase and Extracellular Peptidoglycan

Author

Balraadjsing, Payal P., Lund, Lisbeth D., Souwer, Yuri, Zaat, Sebastian A.J., Frøkiær, Hanne, de Jong, Esther C., Balraadjsing, Payal P., Lund, Lisbeth D., Souwer, Yuri, Zaat, Sebastian A.J., Frøkiær, Hanne, and de Jong, Esther C.

Abstract

Staphylococcus aureus has evolved different strategies to evade the immune response, which play an important role in its pathogenesis. The bacteria express and shed various cell wall components and toxins during different stages of growth that may affect the protective T cell responses to extracellular and intracellular S. aureus However, if and how the dendritic cell (DC)-mediated T cell response against S. aureus changes during growth of the bacterium remain elusive. In this study, we show that exponential-phase (EP) S. aureus bacteria were endocytosed very efficiently by human DCs, and these DCs strongly promoted production of the T cell polarizing factor interleukin-12 (IL-12). In contrast, stationary-phase (SP) S. aureus bacteria were endocytosed less efficiently by DCs, and these DCs produced small amounts of IL-12. The high level of IL-12 production induced by EP S. aureus led to the development of a T helper 1 (Th1) cell response, which was inhibited after neutralization of IL-12. Furthermore, preincubation with the staphylococcal cell wall component peptidoglycan (PGN), characteristically shed during the exponential growth phase, modulated the DC response to EP S. aureus PGN preincubation appeared to inhibit IL-12p35 expression, leading to downregulation of IL-12 and an increase of IL-23 production by DCs, enhancing Th17 cell development. Taken together, our data indicate that exponential-phase S. aureus bacteria induce a stronger IL-12-dependent Th1 cell response than stationary-phase S. aureus and that this Th1 cell response shifted toward a Th17 cell response in the presence of PGN.

Published
2019

9. Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity

Author

Dhawan, Shobhit, primary, De Palma, Giada, additional, Willemze, Rose A., additional, Hilbers, Francisca W., additional, Verseijden, Caroline, additional, Luyer, Misha D., additional, Nuding, Sabine, additional, Wehkamp, Jan, additional, Souwer, Yuri, additional, de Jong, Esther C., additional, Seppen, J., additional, van den Wijngaard, René M., additional, Wehner, Sven, additional, Verdu, Elena, additional, Bercik, Premek, additional, and de Jonge, Wouter J., additional

Published
2016
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11. Class II-associated invariant chain peptide down-modulation enhances the immunogenicity of myeloid leukemic blasts resulting in increased CD4+ T-cell responses

Author

Van Luijn, Marvin M., Chamuleau, Martine E.D., Thompson, James A., Ostrand-Rosenberg, Suzanne, Westers, Theresia M., Souwer, Yuri, Ossenkoppele, Gert J., Van Ham, S. Marieke, Van De Loosdrecht, Arjan A., Van Luijn, Marvin M., Chamuleau, Martine E.D., Thompson, James A., Ostrand-Rosenberg, Suzanne, Westers, Theresia M., Souwer, Yuri, Ossenkoppele, Gert J., Van Ham, S. Marieke, and Van De Loosdrecht, Arjan A.

Abstract

Disease recurrence in patients with acute myeloid leukemia may be partially explained by the escape of leukemic blasts from CD4+ T-cell recognition. The current study investigates the role of aberrant HLA class II antigen presentation on leukemic blasts by determining both the clinical and functional impact of the class II-associated invariant chain peptide (CLIP). Design and Methods The levels of expression of CLIP and HLA-DR on blood and bone marrow samples from 207 patients with acute myeloid leukemia were correlated with clinical outcome. Irradiated CLIP- and CLIP+ leukemic blasts were compared for their ability to induce CD4+ T cells during mixed leukocyte reactions. To discriminate between these blasts, we down-modulated CLIP expression on myeloid leukemic cell lines by RNA interference of the invariant chain, a chaperone protein critically involved in HLA-DR processing, and performed flow cytometric sorting for their isolation from primary acute myeloid leukemia samples. Results We found that patients with leukemic blasts characterized by a high amount of HLA-DR occupied by CLIP (relative amount of CLIP) had a significantly shortened disease-free survival. The clear reductions in amount of HLA-DR occupied by CLIP on blasts of the THP-1 and Kasumi-1 myeloid leukemic cell lines after treatment with invariant chain short interfering RNA resulted in enhanced rates of allogeneic CD4+ T-cell proliferation. Similar findings were obtained in an autologous setting, in which there were strong increases in proliferation of remission CD4 + T cells stimulated with CLIP--sorted leukemic blasts from HLA-DR+ acute myeloid leukemia patients, in contrast to CLIP+-sorted leukemic blasts from the same patients. Conclusions These data highlight the relevance of CLIP expression on leukemic blasts and the potential of CLIP as a target for immunomodulatory strategies to enhance HLA

Published
2010

12. Selective Infection of Antigen-Specific B Lymphocytes by Salmonella Mediates Bacterial Survival and Systemic Spreading of Infection

Author

Souwer, Yuri, primary, Griekspoor, Alexander, additional, de Wit, Jelle, additional, Martinoli, Chiara, additional, Zagato, Elena, additional, Janssen, Hans, additional, Jorritsma, Tineke, additional, Bar-Ephraïm, Yotam E., additional, Rescigno, Maria, additional, Neefjes, Jacques, additional, and van Ham, S. Marieke, additional

Published
2012
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16. Myeloid Leukemic Blasts Use the Endogenous HLA Class I Antigen Processing Machinery for Peptide Loading Onto HLA Class II Molecules: Implications for Immunotherapy.

Author

van Luijn, Marvin M., primary, Chamuleau, Martine E.D., additional, Ressing, Maaike E., additional, Wiertz, Emmanuel J.H.J., additional, Ostrand-Rosenberg, Suzanne, additional, Souwer, Yuri, additional, Zevenbergen, Adri, additional, Ossenkoppele, Gert J., additional, van de Loosdrecht, Arjan A., additional, and van Ham, S. Marieke, additional

Published
2009
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18. Detection of aberrant transcription of major histocompatibility complex class II antigen presentation genes in chronic lymphocytic leukaemia identifiesHLA-DOAmRNA as a prognostic factor for survival

Author

Souwer, Yuri, primary, Chamuleau, Martine E. D., additional, van de Loosdrecht, Arjan A., additional, Tolosa, Eva, additional, Jorritsma, Tineke, additional, Muris, Jettie J. F., additional, Dinnissen-van Poppel, Marion J., additional, Snel, Sander N., additional, van de Corput, Lisette, additional, Ossenkoppele, Gert J., additional, Meijer, Chris J. L. M., additional, Neefjes, Jacques J., additional, and Marieke van Ham, S., additional

Published
2009
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20. TAP- and Proteasome-Dependent Endogenous Antigen Loading of HLA Class II in Leukemic Blasts Introduces a Promising New Target for Generating Leukemia-Specific CD4+ T Cells

Author

van Luijn, Marvin M., primary, Ressing, Maaike E., primary, Wiertz, Emmanuel J.H.J., primary, Zevenbergen, Adri, primary, Chamuleau, Martine E.D., primary, Souwer, Yuri, primary, Ostrand-Rosenberg, Suzanne, primary, Ossenkoppele, Gert J., primary, van de Loosdrecht, Arjan A., primary, and van Ham, S. Marieke, primary

Published
2008
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22. The Nature of Antibacterial Adaptive Immune Responses against Staphylococcus aureusIs Dependent on the Growth Phase and Extracellular Peptidoglycan

Author

Balraadjsing, Payal P., Lund, Lisbeth D., Souwer, Yuri, Zaat, Sebastian A. J., Frøkiær, Hanne, and de Jong, Esther C.

Abstract

Staphylococcus aureushas evolved different strategies to evade the immune response, which play an important role in its pathogenesis. The bacteria express and shed various cell wall components and toxins during different stages of growth that may affect the protective T cell responses to extracellular and intracellular S. aureus. However, if and how the dendritic cell (DC)-mediated T cell response against S. aureuschanges during growth of the bacterium remain elusive.

Published
2019
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25. TAP- and Proteasome-Dependent Endogenous Antigen Loading of HLA Class II in Leukemic Blasts Introduces a Promising New Target for Generating Leukemia-Specific CD4+T Cells

Author

van Luijn, Marvin M., Ressing, Maaike E., Wiertz, Emmanuel J.H.J., Zevenbergen, Adri, Chamuleau, Martine E.D., Souwer, Yuri, Ostrand-Rosenberg, Suzanne, Ossenkoppele, Gert J., van de Loosdrecht, Arjan A., and van Ham, S. Marieke

Abstract

According to the classical HLA class II antigen presentation pathway, exogenous antigens are processed in the endosomal/lysosomal pathway and associate with HLA class II after exchange with the class II-associated invariant chain peptide (CLIP). For this reason, the relative amount of CLIP presented by HLA-DR (DR) molecules (CLIP/DR amount) can be considered as an indicator for HLA class II antigen loading. Previously, we showed that Invariant Chain (Ii) down-modulation in the Kasumi-1 and THP-1 AML cell lines led to marked declines in CLIP/DR amount [Van Luijn et al., Haematologica 2008; 93(s1), Abstract 0029]. In addition, the total amount of cell surface-expressed DR was reduced on Kasumi-1 blasts, in line with the need of Ii for the transport of newly synthesized HLA class II molecules into the endosomal/lysosomal pathway. Surprisingly, in THP-1 blasts, Ii down-modulation hardly affected DR expression at the cell surface. In the present study, we further explored the Ii-independent pathway of HLA class II antigen presentation in leukemic blasts. Not only in the THP-1, but also in another AML cell line, the KG-1, Ii down-modulation had no effect on DR expression levels, as determined by flow cytometry. Since DR expression does require peptide binding, Ii-independency in these AML blasts may be achieved by endogenous antigen loading in the endoplasmic reticulum (ER). To test this hypothesis, supply of endogenously derived peptides into the ER was blocked by viral proteins interfering with the function of the transporter associated with antigen processing (TAP). As expected, TAP inhibition in KG-1 blasts by the viral UL49.5 protein (which changes the conformation of TAP and mediates its degradation) resulted in a strong down-regulation (7.7-fold) of HLA class I. Strikingly, TAP inhibition also induced a clear DR−KG-1 blast population (52.3% of total; MFI=1.4) next to the original DR+KG-1 blast population (36.5% of total; MFI=288.9), demonstrating that DR expression is partly TAP-dependent in KG-1 blasts. Upon sorting of both populations, TAP−DR−blasts had a decreased expression of intracellular Ii as compared to TAP−DR+blasts (3.9-fold) and wild type blasts (4.7-fold). Additionally, confocal microscopy revealed that in TAP−DR+blasts, DR localised to the cell surface, indicating that Ii is able to rescue cell surface expression of DR. Indeed, Ii down-modulation in TAP−DR+blasts caused a 2.3-fold decline in DR expression. The observed differences in TAP, Ii and DR expression between these KG-1 variants were confirmed by Western blot analysis. Furthermore, blocking of proteasome function by the specific inhibitors MG-132 and Bortezomib also caused a marked decrease of DR expression on KG-1 blasts (MFI declined from 289.2 to respectively 76.4 and 114.5). Accompanying reduction in HLA class I levels ascertained specific proteasome inhibition. This confirmed that at least part of the antigens presented by DR on KG-1 blasts was derived from endogenous sources. Similar results were obtained with THP-1 blasts, as both TAP and proteasome inhibition clearly affected DR expression. In line with our observations that in Kasumi-1 blasts, DR expression is Ii-dependent, addition of the TAP and proteasome inhibitors to Kasumi-1 blasts did not affect cell surface expression of DR. In conclusion, our data reveal an alternative Ii-independent, but TAP- and proteasome-dependent cross-presentation pathway in different AML cell lines, which involves HLA class II loading of endogenous antigens in the ER. Therefore, this alternative pathway may serve as a potent immunomodulatory target in leukemic blasts to activate CD4+T cells specific for a broad range of leukemia-associated antigens.

Published
2008
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26. Class II-associated invariant chain peptide down-modulation enhances the immunogenicity of myeloid leukemic blasts resulting in increased CD4+ T-cell responses.

Author

van Luijn MM, Chamuleau ME, Thompson JA, Ostrand-Rosenberg S, Westers TM, Souwer Y, Ossenkoppele GJ, van Ham SM, and van de Loosdrecht AA

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Antigen Presentation, Antigens, Differentiation, B-Lymphocyte chemistry, Antigens, Differentiation, B-Lymphocyte genetics, Blast Crisis, Female, Histocompatibility Antigens Class II chemistry, Histocompatibility Antigens Class II genetics, Humans, Leukemia, Myeloid, Acute pathology, Lymphocyte Activation, Male, Middle Aged, Prognosis, RNA, Small Interfering pharmacology, Tumor Cells, Cultured, Young Adult, Antigens, Differentiation, B-Lymphocyte metabolism, CD4-Positive T-Lymphocytes immunology, HLA-DR Antigens immunology, Histocompatibility Antigens Class II metabolism, Leukemia, Myeloid, Acute immunology
Abstract

Background: Disease recurrence in patients with acute myeloid leukemia may be partially explained by the escape of leukemic blasts from CD4(+) T-cell recognition. The current study investigates the role of aberrant HLA class II antigen presentation on leukemic blasts by determining both the clinical and functional impact of the class II-associated invariant chain peptide (CLIP)., Design and Methods: The levels of expression of CLIP and HLA-DR on blood and bone marrow samples from 207 patients with acute myeloid leukemia were correlated with clinical outcome. Irradiated CLIP(-) and CLIP(+) leukemic blasts were compared for their ability to induce CD4(+) T cells during mixed leukocyte reactions. To discriminate between these blasts, we down-modulated CLIP expression on myeloid leukemic cell lines by RNA interference of the invariant chain, a chaperone protein critically involved in HLA-DR processing, and performed flow cytometric sorting for their isolation from primary acute myeloid leukemia samples., Results: We found that patients with leukemic blasts characterized by a high amount of HLA-DR occupied by CLIP (relative amount of CLIP) had a significantly shortened disease-free survival. The clear reductions in amount of HLA-DR occupied by CLIP on blasts of the THP-1 and Kasumi-1 myeloid leukemic cell lines after treatment with invariant chain short interfering RNA resulted in enhanced rates of allogeneic CD4(+) T-cell proliferation. Similar findings were obtained in an autologous setting, in which there were strong increases in proliferation of remission CD4(+) T cells stimulated with CLIP(-)-sorted leukemic blasts from HLA-DR(+) acute myeloid leukemia patients, in contrast to CLIP(+)-sorted leukemic blasts from the same patients., Conclusions: These data highlight the relevance of CLIP expression on leukemic blasts and the potential of CLIP as a target for immunomodulatory strategies to enhance HLA class II antigen presentation and CD4(+) T-cell reactivity in acute myeloid leukemia.

Published
2010
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