Reassessment of the role of CD8+ T cells in the induction of allograft tolerance by donor-specific blood transfusion

Douillard, Patrice; Vignes, Caroline; Josien, Régis; Chiffoleau, Elise; Heslan, Jean‐Marie; Proust, Valia; Soulillou, Jean‐Paul; Cuturi, María Cristina

doi:10.1002/(sici)1521-4141(199906)29:06<1919::aid-immu1919>3.0.co;2-8

Cited by 26 publications

(6 citation statements)

References 16 publications

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“…There is now a large body of evidence showing that, whereas CD8 + T cells may play a role (17,51–53), CD4 + T cells are the major regulatory population involved in the DST effect (2,4,22). Nevertheless, their mode of action, their compartmentalization and the extent to which they efficiently inhibit effectors or cytotoxic cells, thereby preventing chronic rejection, remains obscure (34,54).…”

Section: Discussionmentioning

confidence: 99%

Functional Compartmentalization Following Induction of Long-Term Graft Survival with Pregraft Donor-Specific Transfusion

Lair

Degauque

Miqueu³

et al. 2007

American Journal of Transplantation

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Long-term survival is achieved in rat recipients by pregraft donor-specific blood transfusion. We characterized the immune compartments in long-term survivors and analyzed them for capacity to transfer tolerance and protect against chronic rejection. Splenocytes and spleen T cells from treated recipients transferred longterm graft survival to 100% of secondary recipients. In contrast, blood transferred graft survival to only 50% of recipients whereas blood T cells had no effect. An unaltered TCR repertoire, an increase in suppressive CD4 + CD25 + T cells, a decrease in antidonor T-cell proliferative response and normal perforin-granzyme levels were the hallmarks of the spleen T cells. Blood T cells were characterized by a strongly altered CD8 + repertoire, normal CD4+ CD25 + T cell number with unchanged antidonor T-cell proliferative response, an activated T-cell phenotype and an increase in perforingranzyme levels. However, following the transfer of blood or spleen cells into secondary recipients, all grafts displayed chronic rejection. These findings provide evidence that distinct compartments play critical roles in DST recipients. Regulatory cells do not accumulate in blood, which appears to be a reservoir for cytotoxic T cells. Spleen T cells, which display a regulatory-like profile and transfer graft survival, are not able to prevent chronic rejection.

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Section: Discussionmentioning

confidence: 99%

Functional Compartmentalization Following Induction of Long-Term Graft Survival with Pregraft Donor-Specific Transfusion

Lair

Degauque

Miqueu³

et al. 2007

American Journal of Transplantation

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“…In addition, altered CDR3-LD were found to be mostly made up of CD8 + T cells. CD8 + T-cell subsets have been shown to have regulatory properties in several animal models as well as in humans (12,25,26). However, there was also a significantly higher level of CD4 + CD25 + T cells (p < 0.05), another T-cell population with putative regulatory properties, in the blood of DF-Tol and Ster patients compared to patients with chronic rejection (20.5 ± 7.3% vs. 10.6 ± 5.2%) (S. Louis et al, submitted for publication).…”

Section: Discussionmentioning

confidence: 99%

Operationally Tolerant and Minimally Immunosuppressed Kidney Recipients Display Strongly Altered Blood T-Cell Clonal Regulation

Brouard

Dupont

Giral

et al. 2005

American Journal of Transplantation

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†These authors contributed equally to this work.Most kidney transplant recipients who discontinue immunosuppression reject their graft. Nevertheless, a small number do not, suggesting that allogeneic tolerance state (referred to operational tolerance) is achievable in humans. So far, however, the rarity of such patients has limited their study. Because operational tolerance could be linked to anergy, ignorance or to an active regulatory mechanism, we analyzed the blood T-cell repertoire usage of these patients. We report on comparison of T-cell selection in drug-free operationally tolerant kidney recipients (or with minimal immunosuppression), recipients with stable graft function, chronic rejection and healthy individuals. The blood T cells of operationally tolerant patients display two major characteristics: an unexpected strongly altered T-cell receptor (TCR) Vb usage and high TCR transcript accumulation in selected T cells. The cytokine transcriptional patterns of sorted T cells with altered TCR usage show no accumulation of cytokine transcripts (IL10, IL2, IL13, IFN-c ), suggesting a state of hyporesponsiveness in these patients. Identification of such a potential surrogate pattern of operational tolerance in transplant recipients under life-long immunosuppression may provide a new basis and rationale for exploration of tolerance state. However, these data obtained in a limited number of patients require further confirmation on larger series.

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“…More recently, increasing evidence has been provided that CD8+ T cells not only represent a powerful pro-inflammatory arm of the adaptive immune system, but, paradoxically, they can play a pivotal role also in suppression of T cell response (64)(65)(66)(67)(68)(69). In this regard, we have recently reported evidence that hepatitis C virus (HCV)-specific CD8+ T cells producing IL-10 can be isolated from livers of patients with chronic hepatitis C. These cells appears to have a pivotal role in controlling the magnitude of immune responses sustaining both a longlasting virus/host symbiosis and a constant pool of memory cells instrumental for providing concomitant immunity.…”

Section: Cd8+ T Cells Can Be Themselves Efficient Regulators Of the Imentioning

confidence: 99%

Mechanisms of CD8+ T cell peripheral tolerance to our own antigens

Marino¹

2005

Front Biosci

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CD8+ T cells represent a powerful arm of the adaptive immunity that is particularly effective against intracellular pathogens. These cells might also participate in the generation and sustenance of autoimmune responses. The escape of a certain number of CD8+ autoreactive T lymphocytes from thymic negative selection occurs normally in all individuals, but this event is rarely associated with the onset of autoimmune diseases. Several peripheral mechanisms have been evolved by the immune system to take control of these potentially harmful self-aggressive cytotoxic CD8+ T cells. In the present review, we will discuss the principal strategies by which the immune system is capable of maintaining CD8+ T cell tolerance to self, thus making them ineffective to harm their own host but still capable to defend the host against foreign invaders.

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Reassessment of the role of CD8+ T cells in the induction of allograft tolerance by donor-specific blood transfusion

Cited by 26 publications

References 16 publications

Functional Compartmentalization Following Induction of Long-Term Graft Survival with Pregraft Donor-Specific Transfusion

Functional Compartmentalization Following Induction of Long-Term Graft Survival with Pregraft Donor-Specific Transfusion

Operationally Tolerant and Minimally Immunosuppressed Kidney Recipients Display Strongly Altered Blood T-Cell Clonal Regulation

Mechanisms of CD8+ T cell peripheral tolerance to our own antigens

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