Rejection, After a Slightly Prolonged Survival Time, of Langerhans Cell-Free Allogeneic Cultured Epidermis Used for Wound Coverage in Humans

Auböck, Josef; Irschick, Eveline U.; Romani, Nikolaus; Kompatscher, Peter; Herold, Reinhard Höpfl Manfred; Schuler, Gerold; Bauer, Michael; Huber, Christoph; Fritsch, Peter

doi:10.1097/00007890-198804000-00013

Cited by 113 publications

(42 citation statements)

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“…Furthermore, as several investigators have consistently found high alloreactive CTL-p frequencies among both naive and memory T cells [1,29], alloreactive CTL-p more likely represent general properties of the entire CTL-p population than CTL-p specific for recall antigens. We and others have also presented evidence for the existence of a close association between frequencies of graft-or host-specific alloreactive CTL-p and the probability of transplant rejection or graft-versus-host disease [3,19,221. Potential mechanisms which may account for cytokine-induced changes of circulating CTL-p frequencies involve peripheral expansion or deletion, thymic recruitment, pooling by alteration of homing properties and dilution with nonlymphoid cells.…”

Section: Discussionmentioning

confidence: 55%

“…CTL-p frequencies reflect the responder status to a specific antigen more sensitively than can be estimated by bulk culture assays [35]. Challenge with specific antigen in vivo leads to either clonal expansion or clonal suppression of the corresponding CTL-p in human blood [3,19,22]. Clonal expansion of CTL-p and differentiation into functional CTL require cytokines as an additional signal [27,32].…”

Section: Introductionmentioning

confidence: 99%

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IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-p)

et al. 1993

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Experimental animal and human in vivo studies have previously demonstrated the impact of exogenous administration of various cytokines on frequencies of circulating myeloid and LAK precursor cells. For the first time we investigated whether exogenous cytokines, in the absence of antigenic challenge, may also influence frequencies of circulating antigen-specific cytotoxic T-lymphocyte precursor cells. We further asked whether triggering of autoimmune pathways as has been reported for several cytokines can be confirmed on the cellular level by demonstration of induction of autoreactive CTL-p. Limiting dilution analysis was used to determine alloreactive CTL-p frequencies in 31 patients with nonhematologic diseases before and after short-term systemic treatment with either rIL-2 (4.8 x 10(6) IU/m2 bid), rIL-3 (2.5, 5.0 or 10.0 micrograms/kg qd), rGM-CSF (5 micrograms/kg qd), rIFN-gamma (200 or 400 micrograms qd), or IFN-alpha (3 or 5 x 10(6) IU qod). Simultaneously, autoreactive CTL-p frequencies were determined by split-well analysis in 25 of these patients. We found that rIL-2 significantly expands the circulating precursor pool of alloreactive CTL (p < 0.05). rIL-3 affected CTL-p frequencies in a dose-dependent fashion. Low and intermediate doses of rIL-3 did not exhibit significant effects, whereas 10 micrograms/kg rIL-3 led to expansion of alloreactive CTL-p in the same order of magnitude as did rIL-2. This effect was statistically significant when compared with rGM-CSF (p < 0.02), which apparently had no influence on alloreactive CTL-p frequencies. In contrast to rIL-2 and rIL-3, exogenous rIFN-gamma markedly reduced the circulating precursor pool of CTL. This again was statistically significant compared with rIFN-alpha (p < 0.03), which, like rGM-CSF, did not exhibit any effects on the level of alloreactive CTL-p. Frequencies of autoreactive CTL-p were invariably below the limit of detection in our system (< 1/300,000). In conclusion, these data demonstrate that (a) short-term systemic administration of rIL-2, rIL-3, and rIFN-gamma differently affects the clone size of circulating precursors of alloreactive CTL in man, while rGM-CSF and rIFN-alpha do not exhibit measurable effects, and (b) none of the cytokines administered is capable of uncovering detectable frequencies of autoreactive CTL-p.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-p)

et al. 1993

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“…However, the LC-free cultured allogeneic epidermal sheets showed only a slightly prolonged survival time (4-5 days) when used as a wound coverage in humans (Aubock et al 1988), which raises doubts that the depletion of LCs in skin grafts might be clinically viable.…”

Section: Depletion Of Donor-derived Dcsmentioning

confidence: 97%

Fundamental Immunology of Skin Transplantation and Key Strategies for Tolerance Induction

Zhou

Wang

Luo

et al. 2013

Arch. Immunol. Ther. Exp.

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Transplantation of allogeneic or xenogeneic skin grafts can evoke strong immune responses that lead to acute rejection of the graft tissues. In this process, donor-derived dendritic cells play crucial roles in the triggering of such immune responses. Both the innate and acquired host immune systems participate in graft rejection. At present, the rejection of skin grafts cannot be well-controlled by ordinary systemic immunosuppression therapy. Although several strategies for the long-term survival of allogeneic or xenogeneic skin grafts have been demonstrated in animal models, the induction of long-term tolerance to skin grafts is still a great challenge in clinical settings. In this article, we review the progress in the understanding of immune responses to skin grafts and discuss the possible methods that can decrease the immunogenicity of graft tissues and improve the survival of skin grafts, especially those included in preoperative pre-treatments.

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“…Despite the absence of leukocytes and Langerhans cells, the findings showed that cultured epidermal allografts are still rejectable. These epidermal substitute allografts are more immunogenic than previously thought (Rouabhia et al 1993, Aubock et al 1988, and Phillips 1991 and therefore exploring an allogeneic, nonrejectable, and readily available skin substitute may provide a better means of improving wound coverage. Our research group hypothesized that IDO expression should overcome these problems and has worked to develop and apply a novel non-rejectable skin substitute to function not only as wound coverage but also as a rich source of wound-healing promoting factors.…”

Section: Role Of Ido Expression In Engraftment Of An Allogeneic Skin mentioning

confidence: 99%

Immuno-modulatory Role of Indoleamine 2, 3-Dioxygenase in Allogeneic Islet and Skin Transplantation

Gill¹,

Jalili²,

Ghahary³

2013

IMMU

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Indoleamine 2, 3-dioxygenase (IDO) is a naturally occurring immunomodulatory agent that has been found to play a key role in preventing rejection of the semi-allogeneic fetus during pregnancy. It is a cytosolic monomeric hemoprotein enzyme that degrades tryptophan, the least available essential amino acid in the body, through the kynurenine metabolic pathway. This causes a regulatory effect on T cells by, as it has been proposed, causing toxic tryptophan metabolites to accumulate and a tryptophan deficient microenvironment to form. By helping with the induction of T cell unresponsiveness, IDO has been shown to establish immune tolerance and control autoreactive immune responses. Thus, the application of IDO's ability to do this may have a huge potential in improving the rates of acceptance of insulin producing islet cell or skin graft transplants in patients suffering from conditions such as type I diabetes or burn injuries, respectively. The discovery of an agent able to do this is especially important since currently used systemic immunosuppressive drugs carry many side effects and cause complications that make the long term use of these agents problematic after transplantation. This review discusses the immunomodulatory role of IDO and the very promising results of studies done by our research group on the application of this enzyme in islet and skin transplantation.

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Rejection, After a Slightly Prolonged Survival Time, of Langerhans Cell-Free Allogeneic Cultured Epidermis Used for Wound Coverage in Humans

Cited by 113 publications

References 0 publications

IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-p)

IL-2, IL-3, and IFN-gamma differently affect in vivo frequencies of circulating precursors of cytotoxic T lymphocytes (CTL-p)

Fundamental Immunology of Skin Transplantation and Key Strategies for Tolerance Induction

Immuno-modulatory Role of Indoleamine 2, 3-Dioxygenase in Allogeneic Islet and Skin Transplantation

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