Surface Molecules That Drive T Cell Development In Vitro in the Absence of Thymic Epithelium and in the Absence of Lineage-Specific Signals

Cibotti, Ricardo; Punt, Jennifer A.; Dash, Krishna S; Sharrow, Susan O.; Singer, Alfred

doi:10.1016/s1074-7613(00)80327-1

Cited by 101 publications

(107 citation statements)

References 45 publications

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“…1 and 2) (21, 22), indicating that IM effectively mimics the calcium signal induced by TCR-and accessory molecule-mediated stimulation. Indeed, in accord with the IM/PMA-induced thymocyte differentiation, it has been reported that stimulation of isolated CD4 ϩ CD8 ϩ thymocytes by cross-linking of TCR and some of the accessory molecules overnight, followed by culturing without stimulation, results in the differentiation and commitment of the cells to the CD4-T cell lineage (53).…”

Section: Cd8mentioning

confidence: 86%

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Adachi¹,

Amasaki²,

Miyatake³

et al. 2000

Journal of Biological Chemistry

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Differentiation of immature CD4؉ CD8 ؉ thymocytes to mature CD4 ؉ or CD8 ؉ T cells is induced by positive selection and appears to involve calcineurin-dependent activation of NFAT, a family of transcription factors. NFATx is predominantly expressed in CD4 ؉ CD8 ؉ thymocytes, whereas NFATp and NFATc are expressed at much lower levels in the thymus than in mature T cells. However, how or when each NFAT member is involved in the differentiation pathway is unclear. Using an in vitro model system where isolated CD4 ؉ CD8؉ thymocytes can survive and differentiate into semi-mature CD4-lineage T cells, we suggest that low calcineurin activity sustained for approximately 20 h is required for cell survival and differentiation. Accordingly, the DNA binding activity of NFAT slowly increased during the stimulation of 20 h to induce the differentiation. NFATx significantly contributed to the early rise, but the late increase was mostly due to NFATc activation. Meanwhile, the expression of NFATx mRNA decreased and that of NFATc mRNA increased. The DNA-binding activity of NFATp was detectable but low throughout the stimulation. NFATp became dominantly active after the semi-mature T cells differentiated into mature and activated CD4 T cells. These findings suggest that NFATx and NFATc successively play roles in T cell development.

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Section: Cd8mentioning

confidence: 86%

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Adachi¹,

Amasaki²,

Miyatake³

et al. 2000

Journal of Biological Chemistry

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“…Accumulating data from several groups, including that of ours (10), have shown that B7/ CD28 enhances clonal deletion of autoreactive T cells (11)(12)(13)(14). In addition, anti-CD28 Ab promotes differentiation of CD4 ϩ CD8 ϩ double-positive (DP) 4 thymocytes into single-positive (SP) T cells (15,16). Moreover, it has been shown that costimulation is critical for the generation and homeostasis of the CD25 ϩ CD4 ϩ regulatory T cells (17)(18)(19)(20).…”

mentioning

confidence: 99%

B7-CD28 Interaction Promotes Proliferation and Survival but Suppresses Differentiation of CD4−CD8− T Cells in the Thymus

Zheng

Gao

Chang

et al. 2004

The Journal of Immunology

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Costimulatory molecules play critical roles in the induction and effector function of T cells. More recent studies reveal that costimulatory molecules enhance clonal deletion of autoreactive T cells as well as generation and homeostasis of the CD25+CD4+ regulatory T cells. However, it is unclear whether the costimulatory molecules play any role in the proliferation and differentiation of T cells before they acquire MHC-restricted TCR. In this study, we report that targeted mutations of B7-1 and B7-2 substantially reduce the proliferation and survival of CD4−CD8− (double-negative (DN)) T cells in the thymus. Perhaps as a result of reduced proliferation, the accumulation of RAG-2 protein in the DN thymocytes is increased in B7-deficient mice, which may explain the increased expression of TCR gene and accelerated transition of CD25+CD44− (DN3) to CD25−CD44− (DN4) stage. Qualitatively similar, but quantitatively less striking effects were observed in mice with a targeted mutation of CD28, but not CTLA4. Taken together, our results demonstrate that the development of DN in the thymus is subject to modulation by the B7-CD28 costimulatory pathway.

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“…In agreement with the two-signal hypothesis for T cell activation it has been shown that interactions between the TCR and MHC-peptide complexes are not enough to induce complete maturation of CD4 + CD8 + DP thymocytes, suggesting that additional accessory signals are required (Groves et al, 1997;Anderson et al, 1999). In particular, the costimulatory molecules that participate in the initial phases of positive selection have not yet been identified, although some molecules expressed by CD4 + CD8 + DP thymocytes, such as CD2, CD5, CD24, CD28, CD49d, CD81 and thymic shared antigen 1 (TSA-1), have been shown to possess costimulatory activity in vitro in the absence of thymic epithelium, suggesting that these accessory molecules are involved in positive selection (Cibotti et al, 1997;Anderson et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

Kim

et al. 2009

Exp Mol Med

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CD8+ DP and the intermediate thymocytes during thymus regeneration. RT-PCR and Western blot analyses confirmed the presence and elevated levels of 4-1BB and 4-1BBL mRNA and protein in thymocytes during thymus regeneration. We also found that the interaction of 4-1BB with 4-1BBL promoted thymocyte adhesion to thymic epithelial cells. Our results suggest that 4-1BB and 4-1BBL participate in T lymphopoiesis associated with positive selection during recovery from acute thymic involution.

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Surface Molecules That Drive T Cell Development In Vitro in the Absence of Thymic Epithelium and in the Absence of Lineage-Specific Signals

Cited by 101 publications

References 45 publications

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

Successive Expression and Activation of NFAT Family Members during Thymocyte Differentiation

B7-CD28 Interaction Promotes Proliferation and Survival but Suppresses Differentiation of CD4−CD8− T Cells in the Thymus

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

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