Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

Loonen, L.M.P.; Vaessen, L. M. B.; Groeneveld, K.; Jutte, N. H. P. M.; Weimar, Willem; Balk, A. H. M. M.; Mochtar, B.; Claas, Frans H.J.

doi:10.1111/j.1432-2277.1994.tb01452.x

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…In addition, the length and complexity of LDA prevents its use as a routine technique for rejection assessment. A recent report on heart transplantation [18] failed to show differences in peripheral blood donor CTLpf between rejecting and stable patients. Nevertheless, similar overall ranges do not exclude significant withinsubject differences, so it is more adequate to compare pre-and post-Tx data in each patient.…”

Section: Discussionmentioning

confidence: 93%

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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Section: Discussionmentioning

confidence: 93%

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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“…Donor-specific cytotoxic T-cell hyporesponsiveness that develops sometime after kidney (52), heart (44,45,126), or lung (10) transplantation has been described. However, as before, this finding has not been universal (53,(127)(128)(129). Hyporesponsiveness of helper T lymphocytes has also been described (126,130,131), although conflicting data have been reported (132).…”

Section: The Experience Of Immune Monitoring In the Transplant Settingmentioning

confidence: 89%

Immunologic monitoring

Hernandez-Fuentes

Warrens

Lechler

2003

Immunological Reviews

105

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The development of reliable in vitro assays that could allow the quantitation and characterization of anti-donor alloimmune responses has always been a goal in clinical transplantation, both to predict presensitization to the transplanted tissue and to be able to identify rejection without resorting to more invasive tests. With recent development in our understanding of transplantation biology and therapeutics, there is a real expectation that these tests may be used to identify tolerance as much as to predict rejection. The traditional limiting dilution assays still have a contribution to make and are being complemented by an array of tools, such as ELISpot, flow cytometry-based techniques, and microarray analysis. The assays that have been informative, to date, are discussed in this review. This information will lead, at least, to a better understanding of how and when the rejection process occurs. More interestingly, the objective is to apply this information to evaluate tolerance-inducing strategies or to identify patients that have become tolerant to their graft and can be weaned of immunosuppression. Of course sensitive, accurate and specific immunologic monitoring has applications well beyond the field of transplantation.

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“…Monitoring of donor-reactive immune responses has demonstrated that hyporesponsiveness to the direct pathway can develop shortly after solid organ transplantation and is in general associated with stable graft function (Hornick et al, 1998; De Haan et al, 2000). Donor-specific cytotoxic or T cell hyporesponsiveness has been detected in kidney (Ghobrial et al, 1994; Mason et al, 1996; Mestre et al, 1996; Hornick et al, 1998; Baker et al, 2001b), heart (Hu et al, 1994; Hornick et al, 2000; Van Hoffen et al, 2000) and lung (De Haan et al, 2000) transplantation, although this is not a universal finding (Eberspacher et al, 1994; Loonen et al, 1994; Steinmann et al, 1994; Oei et al, 2000). In addition, hyporesponsivessness to donor antigen presented by the indirect pathway has also been described (Salama et al, 2003b).…”

Section: Donor-specific Treg Control Of Alloimmune Responses Followinmentioning

confidence: 99%

Relevance of regulatory T cell promotion of donor-specific tolerance in solid organ transplantation

2012

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Current clinical strategies to control the alloimmune response after transplantation do not fully prevent induction of the immunological processes which lead to acute and chronic immune-mediated graft rejection, and as such the survival of a solid organ allograft is limited. Experimental research on naturally occurring CD4+CD25highFoxP3+ Regulatory T cells (Tregs) has indicated their potential to establish stable long-term graft acceptance, with the promise of providing a more effective therapy for transplant recipients. Current approaches for clinical use are based on the infusion of freshly isolated or ex vivo polyclonally expanded Tregs into graft recipients with an aim to redress the in vivo balance of T effector cells to Tregs. However mounting evidence suggests that regulation of donor-specific immunity may be central to achieving immunological tolerance. Therefore, the next stages in optimizing translation of Tregs to organ transplantation will be through the refinement and development of donor alloantigen-specific Treg therapy. The altering kinetics and intensity of alloantigen presentation pathways and alloimmune priming following transplantation may indeed influence the specificity of the Treg required and the timing or frequency at which it needs to be administered. Here we review and discuss the relevance of antigen-specific regulation of alloreactivity by Tregs in experimental and clinical studies of tolerance and explore the concept of delivering an optimal Treg for the induction and maintenance phases of achieving transplantation tolerance.

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Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

Cited by 4 publications

References 7 publications

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

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

Immunologic monitoring

Relevance of regulatory T cell promotion of donor-specific tolerance in solid organ transplantation

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