Sequential Analysis of the Thymocyte Differentiation in Fully Allogeneic Bone Marrow Chimera in Mice. II. Further Characterization of the CD4+ or CD8+ Single Positive Thymocytes

Arase, Hisashi; Fukushi, Noriko; Hatakeyama, Susumi; Ogasawara, Kunio; Iwabuchi, Kazuya; Iwabuchi, Chikako; Negishi, Izumi; Good, Robert A.; Onoé, Kazunori

doi:10.1016/s0171-2985(11)80326-8

Cited by 18 publications

(3 citation statements)

References 34 publications

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“…We used fetal thymus as a source of thymic progenitors because they contained greater numbers of immature thymocytes than were present in established SCID-hu grafts. The differentiation of hematopoetic stem cells to mature T cells after their injection into heterologous thymic grafts has been demonstrated (50), indicating the ability of thymocyte progenitors, mismatched with respect to their expression of HLA antigens compared with the recipient thymus (51), to differentiate normally in SCID-hu mice (6,48). In these experiments, the mature, donor-derived thymocytes had normal phenotypes and were tolerant to the HLA presented by the thymic-host stromal environment (52).…”

Section: Discussionmentioning

confidence: 99%

Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate.

Kraft

Weissman

Waller

1993

The Journal of Experimental Medicine

112

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SummaryHuman thymocyte differentiation was examined by injecting fetal thymic progenitor populations into human thymic xenografts in SCID-hu mice. Thymic progenitors were fluorescently labeled with the lipophilic dye PKH2. The phenotypes of their progeny could be identified by flow cytometric analysis of cells with a very high fluorescent PKH2 signal. Intrathymic injection of purified triple negative (TN) CD3-4-8-thymocytes resulted in the sequential appearance of CD3-4+8 -, CD3-4+8 +, and CD3+4+8 + cells, with the subsequent appearance of anal1 numbers of phenotypically mature CD3 +4 + 8-and CD3 + 4-8 + ceils over a 4-d period. Sorted CD3-4+8 -thymocytes injected intrathymically rapidly differentiated to CD4+8 + cells. CD4 + 8 + fetal thymocytes in cell eycle differentiated into phenotypically mature CD3 +4+8-and CD3 +4-8 + populations, whereas nondividing CD4+8 + cells failed to differentiate after intrathymic transfer. The number of cell divisions that occurred between the injection of TN thymocytes and their progeny at different time points was estimated based on the decrease in the intensity of the PKH2 label. The average length of the cell cycle for the TN population was calculated to be 24 h. The SCID-hu model thus provides a useful tool for studying the kinetics of cell division and differentiation of human thymocytes in vivo.A major site of T lymphocyte differentiation is the thymus (for a review see reference 1). CD3-4-8-, triple negative (TN) 1 (or in some cases CD3-41~ [2]) thymic progenitors from the bone marrow (3), fetal liver, and yolk sac have been shown in mice (4, 5) and humans (6, 7) to migrate to the thymus where they undergo maturation and differentiation. In vivo studies of murine thymocytes have demonstrated differentiation of TN thymocytes to mature CD3+4+8 -and CD3 +4-8 + single positive populations via immature CD3-4-8 + followed by CD4+8 + intermediates (8, 9). The fate of most developing thymocytes is intrathymic death, either early through a failure of the TCR expressed on the cell surface to be engaged by its self-MHC, or later in maturation through a process by which self-reactive thymocytes are eliminated, termed negative selection (10-13). Before or concomitant to negative selection, CD4+8+3 l~ ceils that are specific for self-MHC undergo positive selection to develop 1Abbreviations used in this paper: APC, allophycocyanin; DP, double positive; NCS, normal calf serum; PI, propidium iodide; SA, Streptavidin; TR, Texas red.into T cells that express high levels of TCR in association with the CD4 or CD8 coreceptor, and which are capable of interacting with antigen bound to self-MHC (10, 14-16). Thymocytes that have successfully passed through positive and negative selection develop into TCR hi T calls with mature phenotypes, emigrate to the periphery, and home to peripheral lymphoid organs (17)(18)(19). The kinetics of call division and differentiation during these processes have been partially defined in murine systems (20)(21)(22)(23), and to our knowledge, have not been described...

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Section: Discussionmentioning

confidence: 99%

Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate.

Kraft

Weissman

Waller

1993

The Journal of Experimental Medicine

112

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“…We found that this subset was relatively frequent in CBA/H mice and although present, was indeed more difficult to identify in some strains: C57BL/10, BALB/c, DBA-2 (this study) and C57BL/6[4]. BM cells from B10 mice were also found to generate CD4+8-3-cells in an AKR thymic environment[21] and a closer analysis of a number of studies reveals their presence[19,[22][23][24][25].…”

mentioning

confidence: 84%

Characterization of immature CD4⁺CD8⁻CD3⁻ thymocytes

Hugo

Waanders²,

Boyd³

et al. 1991

Eur J Immunol

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Previously we have described (Hugo, P. et al., Int. Immunol. 1990. 2: 209) an immature CD4+CD8-CD3- thymocyte subset which is thought to be the counterpart of the CD4-CD8+CD3- subset. In this study we show that the ontogeny of these two subsets is parallel in fetal thymic organ culture. Extensive phenotypic characterization of CD4+CD8-CD3- cells reveals that they closely resemble CD4-CD8+CD3- thymocytes being: HSAhigh, Thy-1high, interleukin 2 receptor alpha chain negative, CD44-, H-2K+/-, CD5low, MEL-14low/intermediate, CD2+, LFA-1+ and MTS 35+. Finally, we show that the proportion of CD4+CD8-CD3- thymocytes is highly variable between mouse strains.

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“…Phenotypic heterogeneity among mouse single-positive thymocytes has been described with respect to expression of heat-stable antigen (HSA) [5,61 and NK1.l [7]. Activation of HSAhIgh and HSA'" CD4'CD8-thymocytes reveals marked differences in their cytokine repertoires.…”

Section: Introductionmentioning

confidence: 99%

CD4⁺CD8⁻ thymocytes that express L‐selectin protect rats from diabetes upon adoptive transfer

et al. 1996

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Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50% of pre-diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8- thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8- thymocytes. In this study, we show that L-selectin is expressed by 50-60% of all CD4+CD8- thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8- thymocytes was mediated almost entirely by the L-selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin- CD4+CD8- thymocytes failed to mediate these responses. These data indicate that CD4+CD8- thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.

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Sequential Analysis of the Thymocyte Differentiation in Fully Allogeneic Bone Marrow Chimera in Mice. II. Further Characterization of the CD4+ or CD8+ Single Positive Thymocytes

Cited by 18 publications

References 34 publications

Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate.

Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate.

Characterization of immature CD4⁺CD8⁻CD3⁻ thymocytes

CD4⁺CD8⁻ thymocytes that express L‐selectin protect rats from diabetes upon adoptive transfer

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Sequential Analysis of the Thymocyte Differentiation in Fully Allogeneic Bone Marrow Chimera in Mice. II. Further Characterization of the CD4+ or CD8+ Single Positive Thymocytes

Cited by 18 publications

References 34 publications

Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate.

Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate.

Characterization of immature CD4+CD8−CD3− thymocytes

CD4+CD8− thymocytes that express L‐selectin protect rats from diabetes upon adoptive transfer

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Characterization of immature CD4⁺CD8⁻CD3⁻ thymocytes

CD4⁺CD8⁻ thymocytes that express L‐selectin protect rats from diabetes upon adoptive transfer