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1. |
Cell-mediated Cytotoxicity in Perforin-less Mice |
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International Reviews of Immunology,
Volume 13,
Issue 1,
1995,
Page 1-14
ClarkWilliam R.,
WalshCraig M.,
GlassAlison A.,
HuangManley T. F.,
AhmedRafi,
MatloubianMehrdad,
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摘要:
We have used a perforin-less (P0) mouse to explore alternate CTL-mediated lytic pathways. P0 mice are unable to overcome an infection with LCMVin vivo.Nevertheless, splenocytes from infected mice show vigorous, antigen-specific cytotoxicity that requires the presence of the Fas antigen on target cells. The Fas lytic pathway is virtually indistinguishable, in terms of kinetics and magnitude of cytotoxicity, from perforin/granzyme-mediated lysis. It is rapidly induced in CTL upon occupation of the TcR, and requires protein synthesis for full expression. Upon removal of the activating signal, the capacity forfas-mediated lysis rapidly disappears. P0 mice infected with LCMV also undergo what appears to be a CD8-mediated immunopathology, and rarely live beyond one month. The precise basis of this pathology is unknown at present. Given the widespread distribution of Fas in mice, particularly on inflamed tissues, the complete failure to clear virus from any tissue or organ is surprising.
ISSN:0883-0185
DOI:10.3109/08830189509061734
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
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2. |
The Function of the CD4 Coreceptor in the Development of T Cells |
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International Reviews of Immunology,
Volume 13,
Issue 1,
1995,
Page 15-27
KilleenNigel,
LittmanDan R.,
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摘要:
T cells with helper activity can be found in mice that lack expression of the CD4 glycoprotein. The CD4 promoter is active in these cells; they respond to antigens presented by MHC class II molecules; they do not express CD8 and they do not depend on MHC class I for their development. By such criteria, these CD8 T cells resemble normal CD4+helper T cells. The development of the helper lineage in CD4-null mice can be potentiated by expression of transgenes that encode either wild type CD4, or a deletion mutant of CD4 that lacks the cytoplasmic tail and therefore cannot interact with the tyrosine kinase p56Ick. These observations suggest that CD4 is not absolutely required for the specification of the helper cell lineage. The role of the CD4 molecule in the development of T cells and possible mechanisms by which it achieves its functions are discussed.
ISSN:0883-0185
DOI:10.3109/08830189509061735
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
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3. |
T Cell Development in CD3-ζMutant Mice |
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International Reviews of Immunology,
Volume 13,
Issue 1,
1995,
Page 29-41
HuangManley T. F.,
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摘要:
Increasing evidence points to multiple pathways of T lymphocyte development. The well characterized thymus-dependent pathway gives rise to T cells bearing TCRαβheterodimers and either CD4 or CD8αβco-receptors. T cells of this lineage populate peripheral lymphoid compartments including lymph nodes, spleen, skin, and Peyer's patches. By comparison, factors which govern extrathymic T cell development are poorly understood. A variety of experiments have shown that intestinal intraepithelial lymphocytes (IELs) develop outside of the thymic environment, e.g., in the gut of nude, SCID, andβ2m-/- mutant mice, and after transplanting bone marrow or fetal liver cells into irradiated thymectomized adult mice. This review focuses on the role of the CD3-ζsubunit in the development of both thymically and extrathymically derived T cells as determined by gene-targeting experiments in mice. Data from these and other T cell-related mutations continue to define crucial stages in thymocyte differentiation. Most interestingly, CD3-ζmutant mice contain a unique population of intestinal IELs that develops independently of thymic selective processes and expresses a novel TCR/CD3 complex.
ISSN:0883-0185
DOI:10.3109/08830189509061736
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
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4. |
Lymphocyte Development and Function in T-Cell Receptor and RAG-1 Mutant Mice |
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International Reviews of Immunology,
Volume 13,
Issue 1,
1995,
Page 43-63
MombaertsPeter,
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摘要:
We have used gene targeting in embryonic stem cells to generate mice with mutations in T-cell receptor (TCR) gene-α, TCR-β, TCR-δor the Recombination Activating Gene-1 (RAG-1). TCR-αor TCR-βmutant mice are deficient inαβT cells, but still containγδT cells and B cells. TCR-δmutant mice are deficient inγδT cells, but still containαβT cells and B cells. Mice doubly mutant for TCR-βand TCR-δdo not have any mature T cells, but still have B cells. RAG-1 mutant mice are totally deficient in both mature T cells and B cells. Here, I describe recent studies of thymocyte development in the mutant mice, and I review experiments addressing the function of the immune system of the mutant mice.
ISSN:0883-0185
DOI:10.3109/08830189509061737
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
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5. |
Human Antibodies from Transgenic Mice |
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International Reviews of Immunology,
Volume 13,
Issue 1,
1995,
Page 65-93
LonbergNils,
HuszarDennis,
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摘要:
We have used homologous recombination in ES cells to engineer B cell-deficient mice that are incapable of expressing endogenous immunoglobulin heavy and kappa light chain genes. We find that B cell development in these mutant mice can be rescued by the introduction of human germline-configuration heavy- and kappa light-chain minilocus transgenes. The transgenes rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation in response to antigen stimulation; thus recapitulating both stages of the humoral immune response using human, rather than mouse, sequences. The mice can be immunized; and human sequence, antigen specific, monoclonal antibodies can be obtained using conventional rodent hybridoma technology. These animals are also of interest for studying the normal processes of immunoglobulin gene expression. We discuss the example of heavy chain class switching, which has not been previously observed within an autonomous transgene.
ISSN:0883-0185
DOI:10.3109/08830189509061738
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
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6. |
Introduction |
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International Reviews of Immunology,
Volume 13,
Issue 1,
1995,
Page -
HuszarDennis,
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ISSN:0883-0185
DOI:10.3109/08830189509061733
出版商:Taylor&Francis
年代:1995
数据来源: Taylor
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