T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia

Bacigalupo, Andrea; Valle, Marisa; Podestà, Marina; Pitto, A.; Zocchi, Elena; Flora, Antonio De; Pozzi, Sara; Luchetti, Silvia; Frassoni, Francesco; Lint, Maria Teresa Van; Piaggio, Giovanna

doi:10.1016/j.exphem.2005.05.006

Cited by 110 publications

(90 citation statements)

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“…The BM in AA is characterized by fewer haemopoietic progenitors, higher number of suppressor T cells and limited ability of mesenchymal stem cells to inhibit T-cell function. 28,34,35 Our study has a modest sample size in spite of performing a 10-year analysis from a national referral centre for BM failure syndromes. This is a reflection of the rarity of acquired AA as well as the fact that not all patients are treated with transplantation.…”

Section: Discussionmentioning

confidence: 99%

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Islam

Anoop

Datta-Nemdharry

et al. 2009

Bone Marrow Transplant

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The precise effects of CD34 þ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34 þ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34 þ cell doses. Infusion of less than 2 Â 10 6 /kg of CD34 þ cells was associated with an increased incidence of graft failures (P ¼ 0.03), higher incidence of bacterial infections (P ¼ 0.006) and a delay in the engraftment of neutrophils (P ¼ 0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34 þ count. Other parameters, such as plt engraftment (P ¼ 0.63), red cell (P ¼ 0.94) and plt (P ¼ 0.31) transfusion independence, chimerism, acute and chronic GVHD (P ¼ 1.0) and OS (P ¼ 0.57), were not significantly influenced by the CD34 þ cell dose. These findings are different to the published studies on the relevance of CD34 þ cell dose in allogeneic transplantation for haematological cancers.

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Section: Discussionmentioning

confidence: 99%

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Islam

Anoop

Datta-Nemdharry

et al. 2009

Bone Marrow Transplant

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“…3 Cells were analysed for the Jak-2 mutation by allele-specific PCR 4 and by microelectronic DNA chip that allows automated calculation of the allelic ratio (mutated V617F vs wild type). 6 No differences emerged in the generation of the stromal layer from the different cMPDs. Furthermore, the cases with allelic ratios 450% V617F did not show any disadvantages in the stromal generation.…”

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confidence: 99%

“…5 Moreover, a few data are available in the literature regarding the heterogeneous pattern of response in inhibiting T-cell proliferation by cultured BM-MSCs from patients with hematological malignancies. 6 In this study, the expression of human leukocyte antigen (HLA), major histocompatibility complex (MHC) class I and II were investigated on in vitro cultured BM-derived MSCs, based on the notion that either undifferentiated or differentiated MSCs express intermediate levels of HLA class I, but do not express the class II molecules. 7 However, it is known that HLA-DR expression by MSCs can be induced by stimulation with interferon g. Interestingly, both undifferentiated and differen-tiated MSCs do not express costimulatory molecules such as B7-1, B7-2, CD40 or CD40L and fail to elicit proliferation of allogeneic lymphocytes.…”

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confidence: 99%

Aberrant expression of HLA-DR antigen by bone marrow-derived mesenchymal stromal cells from patients affected by acute lymphoproliferative disorders

et al. 2006

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tic stem cells. 3 As a single activating mutation in Janus kinase (JAK-2) is considered a very good new marker of clonality in chronic myeloproliferative syndromes (cMPDs), 4 we determined whether the marrow microenvironment is an abnormal stromal compartment carrying the JAK-2 mutation. After obtaining informed consent, we generated bone marrow mesenchymal cells 5 from 20 patients (10 with polycythemia vera, five with essential thrombocythemia and five with idiopathic myelofibrosis) carrying the V617F mutation (Table 1). After a median of 2 months, nHSC were detached and analysed with direct fluorescence for expression of CD45-FITC, CD90-FITC, CD105-FITC (Beckman-Coulter Corporation, Hialeah, FL, USA) and STRO1-PE (Caltag Laboratories, Burlingame, CA, USA) by Epics XL cytometer (Coulter). Polymerase chain reaction (PCR) analysis determined CD45 mRNA expression. 3 Cells were analysed for the Jak-2 mutation by allele-specific PCR 4 and by microelectronic DNA chip that allows automated calculation of the allelic ratio (mutated V617F vs wild type). 6 No differences emerged in the generation of the stromal layer from the different cMPDs. Furthermore, the cases with allelic ratios 450% V617F did not show any disadvantages in the stromal generation. In 15/ 20 cases, flow cytometry analysis revealed that nHSC were negative for CD45 and positive for CD90, CD105 and STRO-1. The other five cases still had residual haematopoietic cells as shown by 1-2% positivity for CD45 at immunophenotyping and strong PCR positivity for CD45 mRNA expression. Five other cases had faint positivity at PCR and 10 were negative. The distribution of CD45 PCR-positive/negative cases was not disease specific. V617F Jak-2 mutation analysis demonstrated that the mutation was not present in the 10 cases that were CD45 negative at immunophenotyping and PCR. A faint positivity emerged in cases with only mRNA positivity at CD45 PCR. The mutation was strongly present in the five cases that were CD45 positive by cytofluorimetry analysis and/or PCR. All JAK-2-positive cases were treated with leucyl-leucine methyl ester, the antilysosomal compound 5 that induces selective depletion of monocyte-macrophages. After treatment, all cases were JAK-2 negative. Macrophages persisting long term in cultures may account for the false positive results reported by Singer et al. 2 These data strongly suggest nHSC do not form part of the malignant clone in cMPDs and support the finding that haematopoietic and stromal cells are not derived from a common stem-cell precursor.

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“…Одним из механизмов снижения супрессор-ной активности МСК является подавление в них экспрессии Jagged-1 (лиганда для Notch рецеп-тора на Т-клетках), индуцированное лигандами для TLR3 и TLR4. Сниженная способность МСК подавлять пролиферацию Т-лимфоцитов была описана у больных с апластической анемией, с иммунной тромбоцитопенической пурпурой и с миелодиспластическим синдромом [4,26,33].…”

Section: клетки-супрессоры в иммунопатогенезеunclassified

Suppressor Cells – The Basis of Immunopathogenesis Autoimmune Diseases

Козлов¹

2016

Med. immunol.

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Адрес для переписки:Козлов Владимир Александрович ФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии» 630099, Россия, г. Новосибирск, ул. Ядринцевская, 14. Тел.: 8 (383) 222-66-27. Факс: 8 (383) 222-70-28. E-mail: vakoz40@yandex.ru Address for correspondence : Kozlov Vladimir A. Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation 630099, Russian Federation, Novosibirsk, Yadrintsevskaya str., Образец цитирования: В.А. Козлов, «Клетки-супрессоры -основа иммунопатогенеза аутоиммунных заболеваний» // Медицинская иммунология, 2016. Т. 18, № 1. С. 7-14. doi: 10.15789/1563-0625-2016-1-7-14 © Козлов В.А., 2016 Immunologiya, 2016, Vol. 18, no. 1, pp. 7-14. doi: 10.15789/1563-0625-2016 Резюме. Обсуждается проблема иммунопатогенеза аутоиммунной патологии. Главное внимание уделяется проблеме участия в патогенезе аутоиммунных заболеваний клеток супрессоров различно-го происхождения (Treg, мезенхимальные стволовые клетки, клетки-супрессоры миелоидного про-исхождения). Большое значение в патогенезе придается процессу гомеостатической пролиферации лимфоцитов. Литературные данные свидетельствуют о том, что при аутоиммунной патологии реги-стрируется снижение функциональной активности обозначенных выше популяций клеток-супрессо-ров, включая Treg, мезенхимальные стволовые клетки, клетки-супрессоры миелоидного происхожде-ния. Именно на фоне снижения активности клеток-супрессоров появляются клоны аутоагрессивных цитотоксических лимфоцитов, синтезируются аутоантитела, которые и обуславливают формирова-ние аутоиммунной патологии. При этом следует учитывать, что все эти процессы протекают на фоне изменений в иммунной системе, индуцированных гомеостатической пролиферацией лимфоидных клеток. Ключевые слова: аутоиммунные реакции, клетки-супрессоры, гомеостаз, пролиферация лимфоцитов SUPPRESSOR CELLS -THE BASIS OF IMMUNOPATHOGENESIS AUTOIMMUNE DISEASESKozlov V.A. Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian FederationAbstract. The issues of immune pathogenesis in autoimmune pathology are discussed in this review. The main attention is drawn to potential pathogenetic role of various suppressor cell populations, including T-regulatory cells, mesenchymal stem cells, myeloid lineage-derived suppressors. Homeostatic lymphocyte proliferation is considered to be of great importance for pathogenesis of autoimmune disorders. Recent data from literature suggest that the autoimmune diseases are characterized by reduced activity of the mentioned suppressor cell populations, thus being a possible prerequisite for development of autoaggressive clones of cytotoxic lymphocytes, increased synthesis of autoantibodies leading to evolving autoimmune pathology. It should be, however, noted, that all these processes are accompanied by changes in the immune system induced by homeostatic proliferation of lymphoid cells.

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T-cell suppression mediated by mesenchymal stem cells is deficient in patients with severe aplastic anemia

Cited by 110 publications

References 29 publications

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Aberrant expression of HLA-DR antigen by bone marrow-derived mesenchymal stromal cells from patients affected by acute lymphoproliferative disorders

Suppressor Cells – The Basis of Immunopathogenesis Autoimmune Diseases

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