Richard Le Blanc | PubMed Health

PubMed2005

T-cell generation by lymph node resident progenitor cells.

In the thymus, 2 types of Lin-Sca-1+ (lineage-negative stem cell antigen-1-positive) progenitors can generate T-lineage cells: c-Kit(hi) interleukin-7 receptor alpha-negative (c-Kit(hi)IL-7Ralpha-) and c-Kit(lo)IL-7Ralpha+. While c-Kit(hi)IL-7Ralpha- progenitors are absent, c-Kit(lo)IL-7Ralpha+ progenitors are abundant in the lymph nodes (LNs). c-Kit(lo)IL-7Ralpha+ progenitors undergo abortive T-cell commitment in the LNs and become arrested in the G1 phase of the cell cycle because they fail both to up-regulate c-myb, c-myc, and cyclin D2 and to repress junB, p16(INK4a), and p21(Cip1/WAF). As a result, development of LN c-Kit(lo)IL-7Ralpha+ progenitors is blocked at an intermediate CD44+CD25lo development stage in vivo, and LN-derived progenitors fail to generate mature T cells when cultured with OP9-DL1 stromal cells. LN stroma can provide key signals for T-cell development including IL-7, Kit ligand, and Delta-like-1 but lacks Wnt4 and Wnt7b transcripts. LN c-Kit(lo)IL-7Ralpha+ progenitors are able to generate mature T cells when cultured with stromal cells producing wingless-related MMTV integration site 4 (Wnt4) or upon in vivo exposure to oncostatin M whose signaling pathway intersects with Wnt. Thus, supplying Wnt signals to c-Kit(lo)IL-7Ralpha+ progenitors may be sufficient to transform the LN into a primary T-lymphoid organ. These data provide unique insights into the essence of a primary T-lymphoid organ and into how a cryptic extrathymic T-cell development pathway can be amplified.

Animals↗

PubMed2002

Relations between standing stability and body posture parameters in adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective study of standing imbalance and body posture in 71 able-bodied girls and subjects with adolescent idiopathic scoliosis was conducted. OBJECTIVE: To test the hypothesis that postural parameters are related to standing stability parameters. SUMMARY OF BACKGROUND DATA: Spinal deformity not only modifies the shape of the trunk, but also changes the relations between body segments affecting posture in scoliotic children. These postural adaptations to the scoliotic curve progression could be linked in part to increased body sway in upright standing. This has not yet been related to specific postural parameters involving the head, trunk, and pelvis in nontreated idiopathic scoliosis. METHODS: The head, trunk, and pelvis orientations of each subject were measured by a Flock of Bird system. An AMTI force platform was used to assess quiet standing stability and to monitor the position and displacement of the center of pressure (COP). The center of mass (COM) excursion was estimated from a biomechanical model using force plate information only. Analyses of variance (ANOVAS) were performed to determine the statistical differences between the scoliotic and nonscoliotic subjects, and backward stepwise multiple regression analyses were performed to identify any correlation between measures of quiet standing stability and body postural parameters RESULTS: The scoliotic group was characterized by a decrease in standing stability. There was an increase in the sway areas measured by the variations of the COP and COM. From the backward stepwise multiple regression analysis, it appears that for the able-bodied girls, the body posture parameters were correlated only with the mean anteroposterior center of pressure (COP(AP)) position. For the scoliotic group, the sway areas and the mean position of the centers of pressure and the COP(AP)-COM(AP) were correlated significantly with body posture parameters. The higher COP-COM differences for the scoliotic group were attributed to a greater neuromuscular demand to maintain standing balance. The coefficients of correlation of the multiple regression analyses ranged from 0.64 to 0.85 for the nonscoliotic group and from 0.55 to 0.72 for the scoliotic group. CONCLUSIONS: The use of backward stepwise multiple correlations highlighted the interaction between several body parameters and their relation to standing stability in both able-bodied girls and scoliotic subjects. The scoliotic group displayed a much larger number of correlations between standing stability and body posture parameters than the nonscoliotic group. Standing imbalance was related to altered body posture parameters measured in the frontal and horizontal planes only. Although the correlation coefficients were relatively high, factors other than body posture parameters appeared related to standing imbalance in adolescent idiopathic scoliosis. These findings support the concept of either a primary or a secondary dysfunction in the postural regulation system of scoliotic subjects.

Adolescent↗