Early Defect Prethymic in Bone Marrow T Cell Progenitors in Athymic<i>nu/nu</i>Mice

Chatterjea-Matthes, Devavani; García‐Ojeda, Marcos E.; Dejbakhsh-Jones, Sussan; Jerabek, Libuse; Manz, Markus G.; Weissman, Irving L.; Strober, Samuel

doi:10.4049/jimmunol.171.3.1207

Cited by 16 publications

(18 citation statements)

References 32 publications

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“…However, the BM counterpart in the nude mouse was unable to generate T cells in vivo, probably due to a BM defective stroma, as suggested by the authors (32). In contrast, we demonstrated that the pre-T population in nude spleen is able to reconstitute the T cell compartment efficiently.…”

Section: Discussioncontrasting

confidence: 40%

“…Moreover, these markers are present with the same intensity on pre-T cells from the BM (15,32) and from adult (16) and fetal blood (23), suggesting that they are stable markers for this lineage. In contrast, IL-7R␣ and CD44 are expressed in a steady state but not after BM graft, indicating that these receptors could be modulated over the course of differentiation into pre-T cells.…”

Section: Discussionmentioning

confidence: 74%

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Identification of an IL-7-Dependent Pre-T Committed Population in the Spleen

Gautreau

Arcangeli

Pasqualetto

et al. 2007

The Journal of Immunology

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Several extrathymic T cell progenitors have been described but their various contributions to the T cell lineage puzzle are unclear. In this study, we provide evidence for a splenic Lin−Thy1.2+ T cell-committed population, rare in B6 mice, abundant in TCRα−/−, CD3ε−/−, and nude mice, and absent in IL-7- and Rag-2-deficient mice. Neither B nor myeloid cells are generated in vivo and in vitro. The incidence of these pre-T cells is under the control of thymus and/or mature T cells, as revealed by graft experiments. Indeed, IL-7 consumption by mature T cells inhibits the growth of these pre-T cells. Moreover, the nude spleen contains an additional Lin−Thy1.2+CD25+ subset which is detected in B6 mice only after thymectomy. We establish that the full pre-T cell potential and proliferation capacity are only present in the c-kitlow fraction of progenitors. We also show that most CCR9+ progenitors are retained in the spleen of nude mice, but present in the blood of B6 mice. Thus, our data describe a new T cell lineage restricted subset that accumulates in the spleen before migration to the thymus.

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Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 74%

Identification of an IL-7-Dependent Pre-T Committed Population in the Spleen

Gautreau

Arcangeli

Pasqualetto

et al. 2007

The Journal of Immunology

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“…In contrast, hemopoietic stem cells from wild-type hosts differentiated into functional CTPs in the bone marrow of irradiated thymectomized wild-type hosts within a few weeks after adoptive transfer (3). These extrathymically derived CTPs were able to develop into mature TCR␣␤ ϩ T cells after transfer into additional irradiated wild-type hosts.…”

Section: Stepwise Development Of Committed Progenitors In the Bonementioning

confidence: 96%

“…These extrathymically derived CTPs were able to develop into mature TCR␣␤ ϩ T cells after transfer into additional irradiated wild-type hosts. The latter experiments demonstrated that CTPs are prethymic (thymus-independent) progenitors (3). Studies of the normal human bone marrow have identified early progenitors with characteristics shared by CTPs and/or CIPs, and are committed to the T cell lineage as judged by the expression of T cell lineagespecific genes, active rearrangement of TCR gene segments, and expression of pre-TCR␣ receptors on the cell surface associated with intracellular CD3 (4).…”

Section: Stepwise Development Of Committed Progenitors In the Bonementioning

confidence: 98%

“…Phenotypic CTPs can be found in the bone marrow of athymic nu/nu mice, but these CTPs are not functional due to abnormalities in the nu/nu bone marrow microenvironment that result in defective differentiation from hemopoietic stem cells (3). In contrast, hemopoietic stem cells from wild-type hosts differentiated into functional CTPs in the bone marrow of irradiated thymectomized wild-type hosts within a few weeks after adoptive transfer (3).…”

Section: Stepwise Development Of Committed Progenitors In the Bonementioning

confidence: 99%

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Stepwise Development of Committed Progenitors in the Bone Marrow That Generate Functional T Cells in the Absence of the Thymus

García‐Ojeda¹,

Dejbakhsh-Jones²,

Chatterjea-Matthes³

et al. 2005

The Journal of Immunology

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We identified committed T cell progenitors (CTPs) in the mouse bone marrow that have not rearranged the TCRβ gene; express a variety of genes associated with commitment to the T cell lineage, including GATA-3, T cell-specific factor-1, Cβ, and Id2; and show a surface marker pattern (CD44+CD25−CD24+CD5−) that is similar to the earliest T cell progenitors in the thymus. More mature committed intermediate progenitors in the marrow have rearranged the TCR gene loci, express Vα and Vβ genes as well as CD3ε, but do not express surface TCR or CD3 receptors. CTPs, but not progenitors from the thymus, reconstituted the αβ T cells in the lymphoid tissues of athymic nu/nu mice. These reconstituted T cells vigorously secreted IFN-γ after stimulation in vitro, and protected the mice against lethal infection with murine CMV. In conclusion, CTPs in wild-type bone marrow can generate functional T cells via an extrathymic pathway in athymic nu/nu mice.

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