Extrathymic Development and Function of Human T-Lymphocytes from Bone Marrow Cells in Vitro

Adibzadeh, Medi; Bühring, Hans Jörg; Daikeler, Thomas; Siegels-Hübenthal, Petra; Owsianowsky, Martin; Schenk, Andrea; Rehbein, Arnika; Schaudt, Kurt; Schlotz, Elke; Pohla, Heike; Pawelec, Graham

doi:10.1006/cimm.1994.1054

Cited by 9 publications

(5 citation statements)

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“…There were no double positive T cells and no TCRl* cells. Cells of the CD3-negative CD7' phenotype could also be found in the periphery, but had slighdy different properties in that approximately 90% of extrathymicaliy-derived T cells from this source were CD4+ (34). All TCC were CD2-*-, CD25-*-, CD45RO+ and lacked CDl 6 or CD56.…”

Section: Establishing a Model Of Extrathymic T-cell Differentiation Imentioning

confidence: 99%

“…Ceils with the phenotype CD3-negative CD7+ were sorted and resorted in the fluorescence-activated ceil sorter (FACS) to >99% purity (33). To exclude the seiection of CD3+ cells which might have downregulated expression of CD3 and the T-cell receptor (TCR), RT-PCR for the TCRPchain was performed on fresMy sorted cells (34). These cells were then subjected to LD cloning under the same conditions as the alloactivated PBMC, except that 1000 U/ml of IL-2 were used instead of 20 U/ml, and the mitogen phytohaemagglutinin (PHA) was included in the culture medium.…”

Section: Establishing a Model Of Extrathymic T-cell Differentiation Imentioning

confidence: 99%

“…Lectin-induced cytotoxieity was common (70%) but no TCC was autoreactive either as measured by cytotoxieity or proliferation. Most TCC contained RT-PCR-detectabie mRNA for IL-2, IL-3, IL-4, IL-5, IL-9 and GM-CSF, but they differed from TCC derived from mature T cells in that none expressed IL-6 and only half expressed IFN-y (34). Therefore, with very few exceptions, these extrathymicaliy-derived T cells appeared similar to cells of the same phenotype generated from thymically-derived mature T cells, and therefore seemed suitable for longevity comparisons with the latter.…”

Section: Establishing a Model Of Extrathymic T-cell Differentiation Imentioning

confidence: 99%

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Human T‐cell clones in long‐term culture as a model of immunosenescence

Pawelec

Rehbein

Haehnel

et al. 1997

Immunological Reviews

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We have consistently observed that like other normal somatic tissue cells, human T lymphocytes manifest a finite proliferative capacity in culture in vitro. When measured in population doublings (PD), this averages about 35 PD for T-cell clones (TCC) derived from mature peripheral T cells of young adults and about 20 PD more for TCC derived from T-cell precursors in their bone marrow. We believe that alterations in surface marker phenotypes and corresponding functional changes observed in these human TCC as they progress through their finite lifespans in vitro can provide valuable information on processes of T-cell immunosenescence in vivo. They may also provide a model system for studying ways of modulating the ageing process to delay or prevent immunosenescence in the elderly and the chronically infected or possibly to accelerate immunosenescence in organ transplantation.

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Section: Establishing a Model Of Extrathymic T-cell Differentiation Imentioning

confidence: 99%

Section: Establishing a Model Of Extrathymic T-cell Differentiation Imentioning

confidence: 99%

Section: Establishing a Model Of Extrathymic T-cell Differentiation Imentioning

confidence: 99%

See 1 more Smart Citation

Human T‐cell clones in long‐term culture as a model of immunosenescence

Pawelec

Rehbein

Haehnel

et al. 1997

Immunological Reviews

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“…Our attempts to generate mature T cells from CD34 ϩ stem cells in vitro in the absence of thymic influence were initially unsuccessful, as other groups had reported previously [7,8]. This failure was in marked contrast to the relative ease with which T cells could be made to differentiate in vitro from CD3-negative CD7 ϩ precursors [17,18]. CD34 ϩ cells are known to differentiate into T cells in vitro, but thus far, all systems have required thymic components to enable this [9].…”

Section: Discussionmentioning

confidence: 99%

“…This failure was in marked contrast to the relative ease with which T cells could be made to differentiate in vitro from CD3-negative CD7 ϩ precursors [17,18]. CD34 ϩ cells are known to differentiate into T cells in vitro, but thus far, all systems have required thymic components to enable this [9].…”

Section: Discussionmentioning

confidence: 99%

Extrathymic T cell differentiation in vitro from human CD34+ stem cells

Pawelec

Müller

Rehbein

et al. 1998

Journal of Leukocyte Biology

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Although it is well established that T cells are derived from CD34 ؉ stem cells in vivo, and that T cells can develop in the absence of a functioning thymus, it has not proven possible thus far to generate human T cells in vitro from CD34 ؉ cells in the absence of any thymic influence. We now present a limiting dilution cloning culture system that supports the differentiation of highly purified human CD34 ؉ cells to CD3 ؉ T cells in vitro in the complete absence of any thymic components. The culture system features the use of a serum-free medium supplemented with a cocktail of cytokines including flt-3 ligand, interleukin-3 (IL-3), stem cell factor (SCF), and IL-2. CD4 ؉ T cell clones capable of mitogen-stimulated proliferation and response to IL-2, and expressing a varied TCR-V␤ repertoire were obtained under these conditions. This culture system therefore supports human T lymphopoiesis in the absence of any thymic influence and may prove useful for the evaluation of extrathymic T cell differentiation in vitro. J. Leukoc. Biol. 64: 733-739; 1998.

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Molecular and cell biological studies of ageing and their application to considerations of T lymphocyte immunosenescence

Pawelec

1995

Mechanisms of Ageing and Development

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Extrathymic Development and Function of Human T-Lymphocytes from Bone Marrow Cells in Vitro

Cited by 9 publications

References 0 publications

Human T‐cell clones in long‐term culture as a model of immunosenescence

Human T‐cell clones in long‐term culture as a model of immunosenescence

Extrathymic T cell differentiation in vitro from human CD34+ stem cells

Molecular and cell biological studies of ageing and their application to considerations of T lymphocyte immunosenescence

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