In:
Neuroimmunomodulation, S. Karger AG, Vol. 14, No. 3-4 ( 2007), p. 213-219
Abstract:
The cellular prion protein (PrP 〈 sup 〉 C 〈 /sup 〉 ) is expressed in the nervous and immune systems. Functionally, PrP 〈 sup 〉 C 〈 /sup 〉 has been suggested to participate in neuron survival, neuritogenesis and T lymphocyte activation. Moreover, PrP 〈 sup 〉 C 〈 /sup 〉 interaction with laminin influences neuronal adhesion and neurite extension. Nevertheless, so far the physiological role of PrP 〈 sup 〉 C 〈 /sup 〉 has not been completely elucidated, particularly in the immune system. The aim of the study was to evaluate the possible participation of PrP 〈 sup 〉 C 〈 /sup 〉 in intrathymic T cell development. We evaluated T cell differentiation markers in thymocytes and peripheral lymphocytes, as well as thymocyte death in PrP 〈 sup 〉 C 〈 /sup 〉 -null or PrP 〈 sup 〉 C 〈 /sup 〉 -overexpressing (Tga20) mice, compared to wild-type controls. In these same animals, we ascertained laminin-driven thymocyte migration. Compared to controls, only marginal differences were found in PrP 〈 sup 〉 C 〈 /sup 〉 -null animals. However, Tga20 mice exhibited a severe thymic hypoplasia, with 10–20% lymphocytes compared to wild-type counterparts. In particular, the frequency of CD4+CD8+ cells was largely reduced, and this was accompanied by a dramatic increase in the frequency of CD4–CD8– thymocytes, which could be as high as 60–65% of the whole-cell suspensions. Moreover, Tga20 mice exhibited an increase in thymocyte death, comprising the CD4+CD8+, as well as CD4+ and CD8+ single-positive cells. Additionally, laminin-driven migration was largely impaired in Tga20 mice, in which we also found a significant decrease in total T lymphocytes in the spleen and lymph nodes. Our results show that PrP 〈 sup 〉 C 〈 /sup 〉 overexpression alters intrathymic T cell development, a defect that likely has a negative impact in the formation of the T cell peripheral pool.
Type of Medium:
Online Resource
ISSN:
1021-7401
,
1423-0216
Language:
English
Publisher:
S. Karger AG
Publication Date:
2007
detail.hit.zdb_id:
1483035-8
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