Ontogenic changes in CD95 expression on human leukocytes: prevalence of T-cells expressing activation markers and identification of CD95−CD45RO+ T-cells in the fetus

Muench, Marcus O.; Bartsch, Eva; Chen, Jeng Chang; Lopoo, John B.; Bárcena, Alicia

doi:10.1016/s0145-305x(03)00081-8

Cited by 13 publications

(13 citation statements)

References 51 publications

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“…We found that loss of CD26 does not clearly distinguish between Sézary and reactive cell populations since both CD26À and CD26 þ populations contain detectable T-plastin, a Sézary-cell-specific mRNA. In healthy individuals, a large proportion of the CD4 þ /CD45RO þ T-cell population show cell surface Fas expression (Miyawaki et al, 1992;Muench et al, 2003), which is consistent with the findings reported here demonstrating Fas expression in at least 95% of the CD3 þ CD4 þ /CD45RO þ T cells. In contrast, loss of Fas expression in 7/10 SS patients affected between 32 and 94% of CD3 þ CD4 þ /CD45RO þ cells (shown in Figure 3b) and was associated with downregulation at the mRNA level.…”

Section: Discussionsupporting

confidence: 91%

Downregulation of Fas Gene Expression in Sézary Syndrome Is Associated with Promoter Hypermethylation

Jones

Wain

Chu

et al. 2010

Journal of Investigative Dermatology

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Sézary Syndrome (SS) is an aggressive leukemic variant of primary cutaneous T-cell lymphoma characterized by the presence of tumor or Sézary cells that generally display a mature memory T-cell immunophenotype. Sézary cells proliferate poorly and therefore their accumulation may be due to defective T-cell homeostasis involving resistance to apoptosis. In this study, we analyzed Fas expression in CD4+ lymphocytes at the mRNA and protein levels in a large cohort of SS patients as compared with healthy controls. Fas mRNA expression was dysregulated in 34/47 patients, with significant under- and overexpression of Fas mRNA detected in 21 and 13 patients respectively (P<0.01). Examination of cell-surface Fas expression showed correlation with the observed downregulation of mRNA in CD4+ T cells. Mutational analysis demonstrated that functional FAS gene mutations are rare. Moreover, 16 SS patients who showed significant under-expression of Fas mRNA also showed significant positional hypermethylation within the FAS CpG island, which was not present in healthy controls or SS patients determined to have normal or overexpression of Fas mRNA. These data demonstrate that dysregulation of Fas expression is a common feature of SS, and provide a rationale for targeted therapies to restore the extrinsic Fas-dependent apoptotic pathway in this malignancy.

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Section: Discussionsupporting

confidence: 91%

Downregulation of Fas Gene Expression in Sézary Syndrome Is Associated with Promoter Hypermethylation

Jones

Wain

Chu

et al. 2010

Journal of Investigative Dermatology

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“…Fetal CD4 + T cells expressed CD25, a component of the interleukin (IL)‐2 receptor, and the authors speculated that these represented anergic auto‐reactive T cells. Our own study confirmed the unique properties of fetal T cells demonstrating the expression of a number of T‐cell markers associated with T‐cell activation at frequencies much higher than at term and, sometimes, even higher than found in adult peripheral blood 28 . We speculated that the presence of a high number of T cells expressing IL‐2 receptors might be indicative of the presence of CD4 + T‐regulatory cells (T regs ), which could play a role in the development of fetal self‐tolerance.…”

Section: Resultssupporting

confidence: 83%

Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation

et al. 2011

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BACKGROUND In utero transplantation (IUT) has the potential to treat birth defects early before full development of the immune system. Relatively small grafts, that are not matched for major histocompatibility antigens, can be delivered even before onset of disease symptoms. IUT of hematopoietic stem cells is usually performed via intraperitoneal injection, yet the fate of donor cells in the peritoneal cavity is not fully understood. We review our recent work and present new data demonstrating that the peritoneum can be a site of ectopic hematopoiesis with implications for IUT and immune tolerance induction. STUDY DESIGN AND METHODS Haplogeneic and allogeneic fetal transplants were performed in mice and engraftment tracked by flow cytometry. Immune tolerance was studied by mixed lymphocyte reactions and skin transplantation. Adult syngeneic murine transplants and xenogeneic human into immunodeficient-mouse transplants were performed to follow hematopoietic retention in the peritoneum and engraftment of the bone marrow. RESULTS Although most transplanted cells rapidly clear the peritoneum, hematopoietic cells and cells with the phenotype of hematopoietic precursors can remain in the peritoneal cavity for months after transplant. The presence of donor cells in the peritoneum can contribute to donor-specific tolerance but sufficient peripheral blood chimerism is required to ensure acceptance of donor skin grafts. CONCLUSION Ectopic hematopoiesis and the survival of stem cells in the peritoneum offers the possibility of better using the peritoneal cavity to delivery stem cells and foster the development of immune tolerance to alloantigens or other foreign antigens.

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“…A few reports indicate that the majority of fetal T cells found at mid-gestation (~16–24 g.w.) have a surface phenotype comparable to that of conventional naïve T cells found in neonates and in adults (10–12). To characterize such cells more completely, we analyzed 18–22 g.w.…”

mentioning

confidence: 72%

Fetal and Adult Hematopoietic Stem Cells Give Rise to Distinct T Cell Lineages in Humans

Mold

Venkatasubrahmanyam

Burt

et al. 2010

Science

389

377

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Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or “layering”) of unique hematopoietic stem cells (HSC) that give rise to distinct lymphocyte lineages at different stages of development. Here, we provide evidence of an analogous “layered” immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSC present at different stages of development. We also provide evidence that the fetal T cell lineage is biased towards immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.

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Ontogenic changes in CD95 expression on human leukocytes: prevalence of T-cells expressing activation markers and identification of CD95−CD45RO+ T-cells in the fetus

Cited by 13 publications

References 51 publications

Downregulation of Fas Gene Expression in Sézary Syndrome Is Associated with Promoter Hypermethylation

Downregulation of Fas Gene Expression in Sézary Syndrome Is Associated with Promoter Hypermethylation

Cellular therapies supplement: the peritoneum as an ectopic site of hematopoiesis following in utero transplantation

Fetal and Adult Hematopoietic Stem Cells Give Rise to Distinct T Cell Lineages in Humans

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