Is there a role for cellular prion protein in intrathymic T cell differentiation and migration?
The cellular prion protein (PrP(C)) is expressed in the nervous and immune systems. Functionally, PrP(C) has been suggested to participate in neuron survival, neuritogenesis and T lymphocyte activation. Moreover, PrP(C) interaction with laminin influences neuronal adhesion and neurite extension. Nevertheless, so far the physiological role of PrP(C) has not been completely elucidated, particularly in the immune system. The aim of the study was to evaluate the possible participation of PrP(C) in intrathymic T cell development. We evaluated T cell differentiation markers in thymocytes and peripheral lymphocytes, as well as thymocyte death in PrP(C)-null or PrP(C)-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(C)-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(C) overexpression alters intrathymic T cell development, a defect that likely has a negative impact in the formation of the T cell peripheral pool.
Terra-Granado
Eugênia
E
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Berbert
Luiz Ricardo
LR
de Meis
Juliana
J
Nomizo
Regina
R
Martins
Vilma Regina
VR
Savino
Wilson
W
Silva-Barbosa
Suse Dayse
SD
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016516:CD4-CD8 Ratio; D002452:Cell Count; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D007154:Immune System Diseases / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D007113:Immunity, Innate / Q000276:immunology*; D007797:Laminin / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018621:PrPC Proteins / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism
D015415:Biomarkers; D007797:Laminin; D018621:PrPC Proteins