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Your search keyword '"Bacchetta, R."' showing total 5 results
Start Over Author "Bacchetta, R." Publisher rockefeller university press
5 results on '"Bacchetta, R."'

4. Human hematopoietic cells and thymic epithelial cells induce tolerance via different mechanisms in the SCID-hu mouse thymus

Author

Bart Vandekerckhove, Maria Grazia Roncarolo, Rosa Bacchetta, Reiko Namikawa, Vandekerckhove, Bae, Namikawa, R, Bacchetta, R, and Roncarolo, MARIA GRAZIA

Subjects
CD4-Positive T-Lymphocytes, T-Lymphocytes, T cell, Immunology, Dose-Response Relationship, Immunologic, Mice, SCID, Thymus Gland, Biology, Epithelium, Clonal deletion, Mice, Interleukin 21, Immune Tolerance, medicine, Animals, Humans, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell, Interleukin 3, HLA-D Antigens, Chimera, Articles, Hematopoietic Stem Cells, Molecular biology, Thymocyte, medicine.anatomical_structure, Liver, Interleukin-2, Lymphocyte Culture Test, Mixed, T-Lymphocytes, Cytotoxic
Abstract

To study the role of thymic education on the development of the human T cell repertoire, SCID-hu mice were constructed with fetal liver and fetal thymus obtained from the same or two different donors. These animals were studied between 7 and 12 mo after transplantation, at which times all thymocytes and peripheral T cells were derived from stem cells of the fetal liver graft. Immunohistology of the thymus grafts demonstrated that thymic epithelial cells were of fetal thymus donor (FTD) origin. Dendritic cells and macrophages of fetal liver donor (FLD) origin were abundantly present in the medullary and cortico-medullary areas. Thymocytes of SCID-hu mice transplanted with liver and thymus of two different donors (FLDA/FTDB animals) were nonresponsive to Epstein-Barr virus-transformed B cell lines (B-LCL) established from both the FLDA and FTDB, but proliferated vigorously when stimulated with third-party allogeneic B-LCL. Mixing experiments showed that the nonresponsiveness to FTDB was not due to suppression. Limiting dilution analysis revealed that T cells reacting with the human histocompatibility leukocyte antigens (HLA) of the FLD were undetectable in the CD8+ T cell population and barely measurable in the CD4+ subset. On the other hand, CD4+ and CD8+ T cells reactive to the HLA antigens of the FTD were readily detectable. These results indicate that FLD-reactive cells were clonally deleted, whereas FTD-reactive cells were not. However, the frequencies of FTD-reactive T cells were consistently twofold lower than those of T cells specific for any third-party B-LCL. In addition, the cytotoxic activity and interleukin 2 production by FTD-specific T cells were lower compared with that of third-party-reactive T cell clones, suggesting that FTD-specific cells are anergic. These data demonstrate that T cells become tolerant to autologous and allogeneic HLA antigens expressed in the thymus via two different mechanisms: hematopoietic cells present in the thymus induce tolerance to "self"-antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal energy and possibly deletion of high affinity clones.

Published
1992
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5. An anti-CD45RO/RB monoclonal antibody modulates T cell responses via induction of apoptosis and generation of regulatory T cells.

Author

Gregori S, Mangia P, Bacchetta R, Tresoldi E, Kolbinger F, Traversari C, Carballido JM, de Vries JE, Korthäuer U, and Roncarolo MG

Subjects
Animals, Apoptosis, CD3 Complex, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Cell Proliferation, Cells, Cultured, Graft Survival, Humans, Islets of Langerhans Transplantation immunology, Mice, Mice, Inbred NOD, Mice, SCID, Microfilament Proteins, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Protein-Tyrosine Kinases, Tetanus Toxoid pharmacology, Antibodies, Monoclonal pharmacology, CD4-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes drug effects, Leukocyte Common Antigens immunology
Abstract

The effects of a chimeric monoclonal antibody (chA6 mAb) that recognizes both the RO and RB isoforms of the transmembrane protein tyrosine phosphatase CD45 on human T cells were investigated. Chimeric A6 (chA6) mAb potently inhibited antigen-specific and polyclonal T cell responses. ChA6 mAb induced activation-independent apoptosis in CD4(+)CD45RO/RB(high) T cells but not in CD8(+) T cells. In addition, CD4(+) T cell lines specific for tetanus toxoid (TT) generated in the presence of chA6 mAb were anergic and suppressed the proliferation and interferon (IFN)-gamma production by TT-specific effector T cells by an interleukin-10-dependent mechanism, indicating that these cells were equivalent to type 1 regulatory T cells. Similarly, CD8(+) T cell lines specific for the influenza A matrix protein-derived peptide (MP.58-66) generated in the presence of chA6 mAb were anergic and suppressed IFN-gamma production by MP.58-66-specific effector CD8(+) T cells. Furthermore, chA6 mAb significantly prolonged human pancreatic islet allograft survival in nonobese diabetic/severe combined immunodeficiency mice injected with human peripheral blood lymphocytes (hu-PBL-NOD/SCID). Together, these results demonstrate that the chA6 mAb is a new immunomodulatory agent with multiple modes of action, including deletion of preexisting memory and recently activated T cells and induction of anergic CD4(+) and CD8(+) regulatory T cells.

Published
2005
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