The Earliest Thymic Progenitors in Adults Are Restricted to T, NK, and Dendritic Cell Lineage and Have a Potential to Form More Diverse TCRβ Chains than Fetal Progenitors

Lü, Min; Tayu, Risa; Ikawa, Tomokatsu; Masuda, Kyoko; Matsumoto, Isamu; Mugishima, Hideo; Kawamoto, Hiroshi; Katsura, Yoshiteru

doi:10.4049/jimmunol.175.9.5848

Cited by 71 publications

(80 citation statements)

References 54 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This finding, together with the fact that no detectable B cell progenitor activity can be found among canonical intrathymic progenitors (4,5), suggests that divergence of B and T potential must occur extrathymically. To evaluate this possibility, we screened blood populations defined by presumptive progenitor markers (c-Kit, Sca-1, Flt3, and IL-7R) for growth capacity and clonality under T or B lineage differentiation conditions in vitro.…”

mentioning

confidence: 87%

“…It now seems that, at least in the postnatal thymus, the truth lies somewhere in between. The earliest intrathymic progenitors have the potential to make T cells, as well as other hemopoietic lineages including dendritic cells and NK cells (4,5), but T lineage differentiation is imposed by exposure to the thymic microenvironment (6), primarily through stimulation of Notch (7,8) via ligands expressed on thymic stromal cells (9). Notably, what early intrathymic progenitors appear to lack is the potential to make B cells (4,5), particularly among those that fulfill all the conventional criteria for T cell progenitors (4).…”

mentioning

confidence: 99%

“…The earliest intrathymic progenitors have the potential to make T cells, as well as other hemopoietic lineages including dendritic cells and NK cells (4,5), but T lineage differentiation is imposed by exposure to the thymic microenvironment (6), primarily through stimulation of Notch (7,8) via ligands expressed on thymic stromal cells (9). Notably, what early intrathymic progenitors appear to lack is the potential to make B cells (4,5), particularly among those that fulfill all the conventional criteria for T cell progenitors (4). It should be noted, however, that multiple types of cells can be found within the thymus, including cells with dual T cell/B cell potential (4,10,11), but in general their relative contributions to the T cell pool remain unclear.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The Blood Contains Multiple Distinct Progenitor Populations with Clonogenic B and T Lineage Potential

Umland

Mwangi

Anderson

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

The thymus is seeded by bone marrow-derived progenitors that circulate in the blood. Multiple cell types can be found in the thymus early after i.v. administration or in steady state, but most fail to satisfy the known characteristics of true T progenitors. Cells that do conform to classical definitions retain multilineage potential, but surprisingly, cannot make B cells. Because acquisition of the T lineage fate among noncommitted progenitors is a lengthy process, the absence of B cell potential in early thymocytes suggests that B and T lineages diverge prethymically. To test this suggestion, we screened numerous presumptive progenitor populations for T cell growth and differentiation potential, as well as for clonogenic T or B cell development. We find that blood and marrow each contain multiple distinct subsets that display growth and differentiation potential consistent with being canonical T progenitors. Assessment of clonogenic potential further shows that although all blood and marrow populations have high T cell cloning potential, no T/non-B cells are apparent. These data suggest that either true thymic reconstitution potential derives from a small T/non-B cell subset of one of these populations, or that most of the cells defined as canonical progenitors within the thymus do not, in fact, reside in the mainstream of T progenitor differentiation.

show abstract

mentioning

confidence: 87%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The Blood Contains Multiple Distinct Progenitor Populations with Clonogenic B and T Lineage Potential

Umland

Mwangi

Anderson

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The time after engraftment (before or after 4 wk) and tissues examined (blood vs marrow) represent additional variables between studies. In any case, myeloid potential is lost in a progressive rather than abrupt manner, given that multipotent progenitors acquire LSP or ELP and then CLP characteristics (50,51).…”

Section: Discussionmentioning

confidence: 99%

Primitive Lymphoid Progenitors in Bone Marrow with T Lineage Reconstituting Potential

Perry

Welner

Kouro

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

Multiple subsets of the bone marrow contain T cell precursors, but it remains unclear which is most likely to replenish the adult thymus. Therefore, RAG-1+ early lymphoid progenitors (RAG-1+ ELP), and CD62L/L-selectin+ progenitors (LSP), as well as common lymphoid progenitors from C57BL6-Thy1.1-RAG-1/GFP mouse bone marrow were directly compared in transplantation assays. The two c-Kithigh populations vigorously regenerated the thymus and were superior to common lymphoid progenitors in magnitude and frequency of thymic reconstitution. Regeneration was much faster than the 22 days described for transplanted stem cells, and RAG-1+ ELP produced small numbers of lymphocytes within 13 days. As previously reported, LSP were biased to a T cell fate, but this was not the case for RAG-1+ ELP. Although RAG-1+ ELP and LSP had reduced myeloid potential, they were both effective progenitors for T lymphocytes and NK cells. The LSP subset overlapped with and included most RAG-1+ ELP and many RAG-1−TdT+ ELP. LSP and RAG-1+ ELP were both present in the peripheral circulation, but RAG-1+ ELP had no exact counterpart among immature thymocytes. The most primitive of thymocytes were similar to Lin−c-KithighL-selectin+TdT+RAG-1− progenitors present in the marrow, suggesting that this population is normally important for sustaining the adult thymus.

show abstract

“…50) which maintains DC and T-cell potentials within the thymic environment. 32,[51][52][53][54][55] There is a reduced number and frequency of early thymic precursors in aged mice 56 and in addition, their capacity to produce thymocytes is decreased. 56 Given that we saw a reduction in the number of CD8a 1 cDC in the ageing thymus, in proportion to the decrease in numbers of thymocytes, this indicates that as mice age, the reduced numbers of early thymic precursors still produce a normal ratio of thymocyte to DC.…”

Section: Discussionmentioning

confidence: 99%

Regeneration of dendritic cells in aged mice

et al. 2010

View full text Add to dashboard Cite

Age-related thymic involution causes a decreased output of thymocytes from the thymus, thereby resulting in impairment of T cell-mediated immunity. While alterations in the T cell and non-haematopoietic stromal compartments have been described, the effects of thymic involution on thymic dendritic cells (DC) are not clearly known. Thymic DC play an essential role in shaping T cell-mediated immune responses by deleting self-reactive thymocytes to establish central tolerance and by inducing regulatory T-cell (Treg) development. It is therefore important to assess the prevalence of and alterations to thymic DC with age, as this may impact on their function. We assessed the numbers and proportions of the three distinct subsets of thymic DC in ageing mice, and showed that these subsets are differentially regulated. This is expected as thymic DC subsets have different origins of development. We further assessed the responses of thymic DC in a regenerative environment, such as that induced by sex-steroid ablation (SSA), and clearly showed that, consistent with global thymus regrowth, all three DC populations increased in numbers and regained their relative proportions to thymocytes after an initial lag period. These findings are important for the clinical translation of thymic regenerative approaches, and indicate that SSA facilitates the maintenance of critical processes such as negative selection and Treg induction through promoting thymic DC regeneration. INTRODUCTIONThe thymus has a central role in the deterioration of the immune system with age due to its natural involution.1 Some thymic decline is initially apparent from as early as the first year in humans, but then thymus undergoes more pronounced degeneration from puberty such that by ,25 years of age, the thymus has decreased to approximately 50% of its size at birth progressing through to ,10% capacity by the fifth and sixth decades.2 While the mechanisms of thymic involution have not been precisely defined, there is a clear correlation with the influence of sex steroids, the removal of which reverses thymic atrophy in animal models. 1,[3][4][5][6][7][8] The progressive decrease in thymus size with age is associated with a loss in thymic epithelial cells and a concomitant decrease in thymopoiesis 9 leading to a reduced thymic output of naive T cells.

show abstract

The Earliest Thymic Progenitors in Adults Are Restricted to T, NK, and Dendritic Cell Lineage and Have a Potential to Form More Diverse TCRβ Chains than Fetal Progenitors

Cited by 71 publications

References 54 publications

The Blood Contains Multiple Distinct Progenitor Populations with Clonogenic B and T Lineage Potential

The Blood Contains Multiple Distinct Progenitor Populations with Clonogenic B and T Lineage Potential

Primitive Lymphoid Progenitors in Bone Marrow with T Lineage Reconstituting Potential

Regeneration of dendritic cells in aged mice

Contact Info

Product

Resources

About