المؤلفون: Tomonori Iyoda, Fumiya Yamaide, Muneo Inaba, Birthe Sauter, Shannon J. Turley, Karsten Mahnke, Margit Pack, Ralph M. Steinman, David Sheff, Marion Subklewe, Ira Mellman, Nina Bhardwaj, Kayo Inaba, Matthew L. Albert

المصدر: The Journal of Experimental Medicine

مصطلحات موضوعية: Immunology, Antigen presentation, chemical and pharmacologic phenomena, major histocompatibility complex–peptide complexes, Major histocompatibility complex, necrosis, Mice, 03 medical and health sciences, 0302 clinical medicine, Phagocytosis, Antigen, MHC class I, Animals, Humans, Immunology and Allergy, Antigen-presenting cell, 030304 developmental biology, Antigen Presentation, Mice, Inbred BALB C, 0303 health sciences, biology, Antigen processing, apoptosis, Histocompatibility Antigens Class II, Articles, Dendritic Cells, Dendritic cell, MHC restriction, Molecular biology, 3. Good health, Mice, Inbred C57BL, biology.protein, immature dendritic cells, 030215 immunology

الوصف: Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-Ab MHC class II presenting a peptide derived from I-Eα. When immature DCs from I-Ab mice were cultured for 5–20 h with activated I-E+ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC–peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DRα includes the same peptide sequence as mouse I-Eα. Antigen transfer was preceded by uptake of B cell fragments into MHC class II–rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1–10 thousand times more efficient in generating MHC–peptide complexes than preprocessed I-E peptide. When we injected different I-E– bearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b114b03f316e446377b7114a47cba49Test
https://doi.org/10.1084/jem.188.11.2163Test

المؤلفون: Birthe Sauter, Wilhelmine Hellman, Anita Reddy, Matthew L. Albert, Mary Feldman, Gilla Kaplan, Nina Bhardwaj, Armin Bender

المصدر: Immunobiology. 198:552-567

مصطلحات موضوعية: Time Factors, viruses, Immunology, Antigen presentation, Apoptosis, Hemagglutinin Glycoproteins, Influenza Virus, Viral Nonstructural Proteins, Biology, Monocytes, Virus, Cell Line, Dogs, Animals, Humans, Immunology and Allergy, Antibody-dependent enhancement, Antigen-presenting cell, Antigens, Viral, Follicular dendritic cells, Histocompatibility Antigens Class I, Interferon-alpha, Dendritic Cells, Hematology, Virology, DC-SIGN, Influenza A virus, Interleukin 12, biology.protein, CD8, T-Lymphocytes, Cytotoxic

الوصف: CD8+ cytolytic T lymphocytes (CTLs) are considered to be critical mediators for resistance to influenza virus infection. We have previously demonstrated that dendritic cells are potent antigen presenting cells in the development of anti-influenza CTLs. Here we identify distinctive features of the interaction of influenza virus with dendritic cells. Exposure of dendritic cells to influenza virus at MOIs of 2-4:1 leads to > 90% infection, as manifested by the expression of the viral proteins HA and NS1. The infection is non-toxic as viral protein expression is sustained for > 2 days with retention of viability, but little infectious virus is produced. Substantial induction of the anti-viral cytokine IFN-alpha also occurs. Influenza infection of macrophages also results in viral protein expression in a majority of cells, and synthesis of IFN-alpha. In contrast to dendritic cells, macrophages display evidence of apoptosis within 10-12 hours, and the majority of cells die within 24-36 hours. During this interval macrophages synthesize > 10-fold higher levels of virus than dendritic cells. Infected dendritic cells but not macrophages, can induce substantial CTL responses from purified blood CD8+ T cells in the absence of exogenous cytokines such as IL-2. Low levels of infection (MOIs of 0.02) are sufficient to generate potent CTL responses. Influenza virus expressing non-cleaved HA does not elicit CTLs indicating that virus must access the cytoplasm of dendritic cells to utilize traditional class I processing pathways. These observations indicate that DCs are distinct in their handling of influenza virus and for the induction of anti-viral immunity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d904b94360f2f2e3d30e6137fb2b3ccTest
https://doi.org/10.1016/s0171-2985Test(98)80078-8

المؤلفون: Birthe Sauter, Nina Bhardwaj, Matthew L. Albert

المصدر: Nature. 392:86-89

مصطلحات موضوعية: Antigen presentation, CD1, Apoptosis, Lymphocyte Activation, Major histocompatibility complex, Monocytes, Cell Line, HLA-A2 Antigen, MHC class I, Humans, Cytotoxic T cell, Antigen-presenting cell, Antigens, Viral, Antigen Presentation, Multidisciplinary, biology, Antigen processing, Macrophages, Histocompatibility Antigens Class I, Cross-presentation, Dendritic Cells, Coculture Techniques, Cell biology, Influenza A virus, Immunology, biology.protein, T-Lymphocytes, Cytotoxic

الوصف: CD8+ cytotoxic T lymphocytes (CTLs) mediate resistance to infectious agents and tumours. Classically, CTLs recognize antigens that are localized in the cytoplasm of target cells, processed and presented as peptide complexes with class I molecules of the major histocompatibility complex (MHC). However, there is evidence for an exogenous pathway whereby antigens that are not expected to gain access to the cytoplasm are presented on MHC class I molecules. The most dramatic example is the in vivo phenomenon of cross-priming: antigens from donor cells are acquired by bone-marrow-derived host antigen-presenting cells (APCs) and presented on MHC class I molecules. Two unanswered questions concern the identity of this bone-marrow-derived cell and how such antigens are acquired. Here we show that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs. Our findings suggest a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of CTLs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5ec8afb24d9a3f9830a2d3341cf09e5Test
https://doi.org/10.1038/32183Test

المؤلفون: Julia Kaufman, Suyan Tian, Howard I. Scher, Mayu O. Frank, Salina Parveen, Susan F. Slovin, Michael J. Morris, Matthew L. Albert, Robert B. Darnell, Nathalie E. Blachère, Mayte Suárez-Fariñas

المساهمون: Laboratory of Molecular Neuro-oncology, Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York], Rockefeller University [New York], Memorial Sloane Kettering Cancer Center [New York], This work was supported by the Burroughs Wellcome Fund and Doris Duke Foundation (MLA), the National Institutes of Health (NIH) (R01 CA85784 to RBD), the Rockefeller University Hospital Clinical and Translational Science Awards (CTSA)(grant UL1 RR024143) from the National Center for Research Resources at the NIH, the Leslie Misrock Memorial Fund, and David H. Koch

المصدر: PLoS ONE
PLoS ONE, Public Library of Science, 2010, 5 (9), pp.e12367. ⟨10.1371/journal.pone.0012367⟩
PLoS ONE, Vol 5, Iss 9 (2010)

مصطلحات موضوعية: Non-Clinical Medicine/Research Methods, Male, MESH: Prostatic Neoplasms/drug therapy, Immunology/Immunomodulation, Cell- and Tissue-Based Therapy, MESH: Dendritic Cells/transplantation, lcsh:Medicine, Apoptosis, Prostate cancer, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Dendritic Cells/cytology, MESH: Cell- and Tissue-Based Therapy, lcsh:Science, Oncology/Prostate Cancer, Aged, 80 and over, MESH: Aged, 0303 health sciences, Multidisciplinary, MESH: Middle Aged, Immunogenicity, Vaccination, Cell Biology/Cellular Death and Stress Responses, Middle Aged, 3. Good health, Prostate-specific antigen, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Research Article, MESH: Cell Line, Tumor, Cancer Vaccines, 03 medical and health sciences, MESH: Prostatic Neoplasms/immunology, Immune system, Cell Line, Tumor, medicine, Humans, MESH: Cancer Vaccines/immunology, 030304 developmental biology, Aged, MESH: Humans, business.industry, MESH: Apoptosis, lcsh:R, Vaccine trial, MESH: Prostate-Specific Antigen/immunology, Prostatic Neoplasms, Dendritic cell, Dendritic Cells, MESH: Vaccination, Prostate-Specific Antigen, medicine.disease, MESH: Male, Immunology, MESH: Cancer Vaccines/therapeutic use, lcsh:Q, Mathematics/Statistics, business, MESH: Female, MESH: Dendritic Cells/immunology

الوصف: Background Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine. Methods and Findings We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination. Conclusions An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. (ClinicalTrials.gov number NCT00289341). Trial Registration ClinicalTrials.gov NCT00289341

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b49bc0e40bb9014ed624e5e024f2501Test
https://hal-pasteur.archives-ouvertes.fr/pasteur-01402097/documentTest

المؤلفون: Charles M. Rice, Giovanna Barba-Spaeth, Randy S. Longman, Matthew L. Albert

المساهمون: Laboratory of Virology and Infectious Disease, Rockefeller University [New York]-Center for the Study of Hepatitis C, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Greenberg Medical Research Institute and the Grand Challenges in Global Health. We are grateful to the donors who participated in this study., Vougny, Marie-Christine, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)

المصدر: The Journal of Experimental Medicine
Journal of Experimental Medicine
Journal of Experimental Medicine, Rockefeller University Press, 2005, 202 (9), pp.1179-84. ⟨10.1084/jem.20051352⟩
Journal of Experimental Medicine, 2005, 202 (9), pp.1179-84. ⟨10.1084/jem.20051352⟩

مصطلحات موضوعية: T-Lymphocytes, Epitopes, T-Lymphocyte, Apoptosis, Epitope, Immunology and Allergy, Neutralizing antibody, Cells, Cultured, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Antigen Presentation, Vaccines, Synthetic, Attenuated vaccine, MESH: Dendritic Cells, Yellow Fever Vaccine, 3. Good health, medicine.anatomical_structure, MESH: Calcium, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Yellow fever virus, medicine.drug, MESH: Cells, Cultured, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Vaccines, Synthetic, T cell, Immunology, Antigen presentation, Yellow fever vaccine, Biology, Vaccines, Attenuated, MESH: Epitopes, T-Lymphocyte, 03 medical and health sciences, Immunity, MESH: Vaccines, Attenuated, medicine, Humans, 030304 developmental biology, MESH: Humans, 030306 microbiology, MESH: Apoptosis, Brief Definitive Report, Dendritic Cells, Virology, MESH: Yellow fever virus, MESH: Yellow Fever Vaccine, MESH: T-Lymphocytes, MESH: Antigen Presentation, biology.protein, Calcium, CD8

الوصف: International audience; The yellow fever (YF) 17D vaccine is one of the most successful live attenuated vaccines available. A single immunization induces both long-lasting neutralizing antibody and YF-specific T cell responses. Surprisingly, the mechanism for this robust immunity has not been addressed. In light of several recent reports suggesting flavivirus interaction with dendritic cells (DCs), we investigated the mechanism of YF17D interaction with DCs and the importance of this interaction in generating T cell immunity. Our results show that YF17D can infect immature and mature human DCs. Viral entry is Ca(2+) dependent, but it is independent of DC-SIGN as well as multiple integrins expressed on the DC surface. Similar to infection of cell lines, YF infection of immature DCs is cytopathic. Although infection itself does not induce DC maturation in vitro, TNF-alpha-induced maturation protects DCs from YF-induced cytopathogenicity. Furthermore, we show that DCs infected with YF17D or YF17D carrying a recombinant epitope can process and present antigens for CD8(+) T cell stimulation. These findings offer insight into the immunologic mechanisms associated with the highly capable YF17D vaccine that may guide effective vaccine design.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65d03e1622480d5d488f4842f61dea9bTest
https://pubmed.ncbi.nlm.nih.gov/16260489Test

المؤلفون: Matthew Spataro, Reiko Akakura, Raymond B. Birge, Shin Akakura, Sukhwinder Singh, Jong-Il Kim, Matthew L. Albert

المصدر: Experimental cell research. 292(2)

مصطلحات موضوعية: rac1 GTP-Binding Protein, Integrins, Phagocyte, Dock180, Phagocytosis, Amino Acid Motifs, Down-Regulation, Apoptosis, Ligands, Mice, medicine, Animals, Humans, Receptors, Vitronectin, Opsonin, RGD motif, Phagocytes, Membrane Glycoproteins, biology, Cell Membrane, Cell Biology, Dendritic Cells, Opsonin Proteins, Milk Proteins, Molecular biology, Cell biology, rac GTP-Binding Proteins, Antibody opsonization, medicine.anatomical_structure, Integrin alpha M, Antigens, Surface, biology.protein, Integrin, beta 6, Oligoribonucleotides, Antisense, Signal Transduction

الوصف: Opsonization of apoptotic cells facilitates recognition by phagocytes for the rapid clearance of potentially inflammatory cellular material. The secreted glycoprotein Milk Fat Globule Factor-E8 (MFG-E8) is a member of this family of bridging molecules and is believed to bind phosphatidylserine (PS) on the dying cell, linking it to integrin receptors on the phagocyte. Here we report the characterization of a functional signaling module involving MFG-E8, alphavbeta5 integrin, and DOCK180 for the activation of Rac1. We show that MFG-E8 and DOCK180 are both expressed in phagocytic-competent primary immature dendritic cells (DCs) and DC2.4 cells, and are potently down-regulated upon DC maturation, consistent with their role in phagocytosis and antigen capture. Coexpression of MFG-E8 with alphavbeta5 integrin potentiated integrin-mediated Rac1 activation, which was abrogated by mutagenesis in the RGD motif in MFG-E8. Moreover, expression of antisense DOCK180 abrogated MFG-E8-alphavbeta5-mediated Rac activation and impaired the phagocytosis of apoptotic cells. These data demonstrate a biochemical link between an opsonin of apoptotic cells, the alphavbeta5 integrin, and the Crk-DOCK180-Rac1 pathway, and importantly, show that MFG-E8 and DOCK180 are expressed according to the functional status of the phagocyte.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa1bb7b15cb9e1d36c72092495f18aabTest
https://pubmed.ncbi.nlm.nih.gov/14697347Test

المؤلفون: Robert B. Darnell, Matthew L. Albert, Mithila Jegathesan

المصدر: Nature immunology. 2(11)

مصطلحات موضوعية: CD4-Positive T-Lymphocytes, Immunoconjugates, T cell, Immunology, Antigen presentation, CD40 Ligand, Priming (immunology), Immunoglobulins, Apoptosis, Cell Communication, Biology, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Abatacept, Interleukin 21, CD28 Antigens, Phagocytosis, Antigens, CD, medicine, Immune Tolerance, Immunology and Allergy, Cytotoxic T cell, Humans, CTLA-4 Antigen, CD40 Antigens, Antigen-presenting cell, Antigens, Viral, Cells, Cultured, Antigen Presentation, Cross-Over Studies, Membrane Glycoproteins, Tumor Necrosis Factor-alpha, Models, Immunological, Cell Differentiation, Dendritic cell, Dendritic Cells, HLA-DR Antigens, Natural killer T cell, Orthomyxoviridae, Antigens, Differentiation, Interleukin-12, Coculture Techniques, Cell biology, medicine.anatomical_structure, Culture Media, Conditioned, Interleukin-1, Signal Transduction

الوصف: In vivo models have shown that tissue-restricted antigen may be captured by bone marrow-derived cells and cross-presented for the tolerization of CD8+ T cells. Although these studies have shown peripheral tolerization of CD8+ T cells, the mechanism of antigen transfer and the nature of the antigen-presenting cell (APC) remain undefined. We report here the establishment of an in vitro system for the study of cross-tolerance and show that dendritic cells (DCs) phagocytose apoptotic cells and tolerize antigen-specific CD8+ T cells when cognate CD4+ T helper cells are absent. Using this system, we directly tested the "two-signal" hypothesis for the regulation of priming versus tolerance. We found that the same CD83+ myeloid-derived DCs were required for both cross-priming and cross-tolerance. These data suggested that the current model for peripheral T cell tolerance, "signal 1 in the absence of signal 2", requires refinement: the critical checkpoint is not DC maturation, but instead the presence of a third signal, which is active at the DC-CD4+ T cell interface.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b681d3f6d827104013748559829aaeadTest
https://pubmed.ncbi.nlm.nih.gov/11685217Test

المؤلفون: Jong-Ii Kim, Raymond B. Birge, Matthew L. Albert

المصدر: Nature cell biology. 2(12)

مصطلحات موضوعية: rac1 GTP-Binding Protein, Integrins, Dock180, Macromolecular Substances, Phagocytosis, Integrin, RAC1, Apoptosis, Proto-Oncogene Proteins, Humans, Receptors, Vitronectin, Cells, Cultured, DNA Primers, biology, Base Sequence, Proteins, Cell Biology, Dendritic Cells, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-crk, Recombinant Proteins, Cell biology, rac GTP-Binding Proteins, ELMO1, αvβ5 integrin, biology.protein, Protein Kinases, HeLa Cells, Signal Transduction

الوصف: Integrin receptors are important for the phagocytosis of apoptotic cells. However, little is known about their function in mediating internalization, as previous studies used blocking antibodies for the inhibition of binding. Here we show that the alphavbeta5 receptor mediates both binding and internalization of apoptotic cells. Internalization is dependent upon signalling through the beta5 cytoplasmic tail, and engagement of the alphavbeta5 heterodimer results in recruitment of the p130cas-CrkII-Dock180 molecular complex, which in turn triggers Rac1 activation and phagosome formation. In addition to defining integrin-receptor signalling as critical for the internalization of apoptotic material, our results also constitute the first evidence in human cells that the CED-2-CED-5-CED-10 complex defined in Caenorhabditis elegans is functionally analagous to the CrkII-Dock180-Rac1 molecular complex in mammalian cells. By linking the alphavbeta 5 receptor to this molecular switch, we reveal an evolutionarily conserved signalling pathway that is responsible for the recognition and internalization of apoptotic cells by both professional and non-professional phagocytes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2f63b2ef778c16e116b6ea6e0948a58Test
https://pubmed.ncbi.nlm.nih.gov/11146654Test

المؤلفون: S. Frieda A. Pearce, Loise M. Francisco, Matthew L. Albert, Pampa Roy, Roy L. Silverstein, Birthe Sauter, Nina Bhardwaj

المساهمون: Laboratory of Cellular Physiology and Immunology and Chris Browne Center, Rockefeller University [New York], University of Granada [Granada], Photonique Fibre et Sources Cohérentes (XLIM-PHOT), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Cancer Institute, New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU)-NYU System (NYU), Supported by National Institutes of Health (NIH) grants HL-42540 and EY-10967 (to S.F.A. Pearce andR.L. Silverstein), NIH MSTP grant GM-07793 (to M.L. Albert), NIH grant AI-39516, and grants from theSLE foundation (to N. Bhardwaj), Universidad de Granada = University of Granada (UGR)

المصدر: Journal of Experimental Medicine
Journal of Experimental Medicine, Rockefeller University Press, 1998, 188 (7), pp.1359-68. ⟨10.1084/jem.188.7.1359⟩
The Journal of Experimental Medicine
Journal of Experimental Medicine, 1998, 188 (7), pp.1359-68. ⟨10.1084/jem.188.7.1359⟩

مصطلحات موضوعية: CD36 Antigens, Integrins, MESH: Immunoglobulins, MESH: Membrane Glycoproteins, Apoptosis, MESH: Histocompatibility Antigens Class I, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, MESH: Phagocytosis, MESH: Antigens, CD, Cells, Cultured, 0303 health sciences, Antigen Presentation, Membrane Glycoproteins, biology, MESH: Dendritic Cells, MESH: Receptors, Vitronectin, phagocytosis, hemic and immune systems, MESH: Integrins, Articles, Cell biology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Cells, Cultured, Immunology, Antigen presentation, Immunoglobulins, Major histocompatibility complex, 03 medical and health sciences, Antigen, Antigens, CD, Humans, Receptors, Vitronectin, Antigen-presenting cell, cross-presentation, 030304 developmental biology, MESH: Humans, Follicular dendritic cells, MESH: Antigens, CD36, Macrophages, MESH: Apoptosis, Histocompatibility Antigens Class I, MESH: Macrophages, Dendritic cell, Dendritic Cells, MESH: Antigen Presentation, biology.protein, CD36, MESH: T-Lymphocytes, Cytotoxic, CD8, 030215 immunology, T-Lymphocytes, Cytotoxic

الوصف: International audience; Dendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8(+) T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the alphavbeta5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the alphavbeta5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the alphavbeta5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00543cba283f9c47a12d17e32ab2908cTest
https://hal-pasteur.archives-ouvertes.fr/pasteur-01402441Test