Extrathymic tolerance of mature T cells: Clonal elimination as a consequence of immunity

Webb, Susan R.; Morris, Claudia R.; Sprent, Jonathan

doi:10.1016/0092-8674(90)90420-j

Cited by 841 publications

(442 citation statements)

References 47 publications

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“…If the liver is not a graveyard for activated cells, this raises the question of where the immune system eventually removes the large number of specific cells that arise during an immune response. The ultimate fate of activated CD8 ϩ T cells may resemble that of CD4 ϩ T cells, which undergo Ag-induced cell death in the peripheral organs where they are activated (65)(66)(67)(68).…”

Section: Discussionmentioning

confidence: 99%

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill

Keating

Yue

Rutigliano

et al. 2007

The Journal of Immunology

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Influenza A virus infection of C57BL/6 mice is a well-characterized model for studying CD8+ T cell-mediated immunity. Analysis of primary and secondary responses showed that the liver is highly enriched for CD8+ T cells specific for the immunodominant H2DbNP366–374 (DbNP366) epitope. Functional analysis established that these liver-derived virus-specific CD8+ T cells are fully competent cytotoxic effectors and IFN-γ secretors. In addition, flow cytometric analysis of early apoptotic cells showed that these influenza-specific CD8+ T cells from liver are as viable as those in the spleen, bronchoalveolar lavage, mediastinal lymph nodes, or lung. Moreover, cytokine profiles of the influenza-specific CD8+ T cells recovered from different sites were consistent with the bronchoalveolar lavage, rather than liver population, being the most susceptible to activation-induced cell death. Importantly, adoptively transferred influenza virus-specific CD8+ T cells from the liver survived and were readily recalled after virus challenge. Together, these results show clearly that the liver is not a “graveyard” for influenza virus-specific CD8+ T cells.

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Section: Discussionmentioning

confidence: 99%

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill

Keating

Yue

Rutigliano

et al. 2007

The Journal of Immunology

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“…The fourth case showed undetectable donor-reactive cytotoxic precursor frequencies at 9 months post-Tx while maintaining intermediate frequency of third-party CTLp. Such hyporesponsiveness could represent a clonal deletion of donor-reactive CTL consecutive to the high allogeneic immune response elicited by the allograft rejection [22]. Low levels of donor-specific helper T cell frequency have been found in some patients with graft failure due to chronic rejection [25].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal study of the frequency of cytotoxic T cell precursors in kidney allograft recipients

Mestre¹,

Massip²,

Bas³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYClonal deletion or inactivation of donor-specific alloreactive cells are important mechanisms that are believed to account for acquired immune tolerance in allograft recipients. Serial assessment of precursor cytotoxic T lymphocyte frequencies (CTLpf) by limiting dilution analysis (LDA) provides information at the clonal level on changes in the alloimmune response of graft recipients. We performed a longitudinal study of 15 cadaveric kidney recipients before and every 3 months throughout the first year after transplantation (Tx). Pre-Tx values of donor CTLpf showed high interindividual variability without a predictive value for the clinical outcome. All patients with well functioning kidneys had decreased CTLpf at 3 months post-Tx in comparison with pre-Tx values. This decrease was donorspecific in four patients and was permanent in two cases throughout the study. Most patients presented decreased anti-donor CTLpf values from 6 to 9 months, whereas a partial recovery of donor CTLpf was observed in three patients. Reversible acute rejection was diagnosed in three patients, and it was associated with a marked increase in anti-donor CTLpf, returning to pre-Tx values by 9 months post-Tx. In addition, one patient with chronic rejection displayed a transient increase in CTLpf 6 months after Tx. The results of this sequential study indicate the establishment of a state of either hyporesponsiveness or functional clonal inactivation, transient or permanent, which could facilitate allograft acceptance.

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“…In contrast, T cells do not react against antigens that are continuously present in lymphoid organs. 55,56 Antigen that is continuously present in secondary lymphoid organs will activate and delete all T cells specific for that antigen. The process of activation followed by physical deletion of the T cells is termed exhaustion.…”

Section: Antigen Dose and Localizationmentioning

confidence: 99%

Principles of tumor immunosurveillance and implications for immunotherapy

Ochsenbein

2002

Cancer Gene Ther

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Although antigen loss variants, major histocompatibility ( MHC ) class I down -regulation, or the expression of inhibitory molecules may explain the failure of immunosurveillance against some tumors, this seems not to apply for many other solid peripheral or lymphohematopoietic tumors. Why then is immunosurveillance so ineffective and can it be improved? This review focuses on one important aspect of tumor immunity, namely the relevance of antigen dose and localization. Immune responses in vivo are induced in organized lymphoid tissues, i.e., in lymph nodes and spleen. The antigen dose that reaches secondary lymphoid organs over time is a crucial parameter that drives antiviral and antitumoral immune responses. Tumors use various strategies to prevent efficient presentation of their antigens in lymphoid organs. A major obstacle to the induction of an endogenous tumor -specific cytotoxic T lymphocyte ( CTL ) response is the inefficient presentation of tumor antigen on MHC class I molecules of professional antigenpresenting cells. Peripheral solid tumors that develop outside lymphoid organs are, therefore, often ignored by the immune system. In other situations, tumors -especially of lymphohematopoietic origin -may tolerize specific CTLs. Understanding tumor immunosurveillance is key to the design of efficient antitumor vaccines. Attempts to improve immunity to tumors include vaccination strategies to ( a ) provide the tumor antigen to secondary lymphoid organs using recombinant viruses or dendritic cells as carriers, ( b ) express costimulatory signals on tumor cells, or ( c ) improve the efficiency of cross -priming.

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Extrathymic tolerance of mature T cells: Clonal elimination as a consequence of immunity

Cited by 841 publications

References 47 publications

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill

Virus-Specific CD8+ T Cells in the Liver: Armed and Ready to Kill

Longitudinal study of the frequency of cytotoxic T cell precursors in kidney allograft recipients

Principles of tumor immunosurveillance and implications for immunotherapy

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