Naslov
MHC class II expression through a hitherto unknown pathway supports T helper cell dependent immune responses: implications for MHC class II deficiency
(MHC class II expression through a hitherto unknown pathway supports T helper cell dependent immune responses:implications for MHC class II deficiency)

Autori
Buch, Thorsten ; Polić, Bojan ; Clausen, Bjoern E. ; Weiss, Susanne ; Akilli, Ozlem ; Chang, Cheong-Hee ; Flavell, Richard ; Schulz, Ansgar ; Jonjić, Stipan ; Waisman, Ari ; Foerster, Irmgard

Izvornik
Blood (0006-4971) 107 (2006), 4; 1434-1444

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Bare Lymphocyte Syndrome; MHC class II; RFX5; CIITA; T helper cells

Sažetak
MHC class II (MHCII) deficiency of Bare Lymphocyte Syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th) cell dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional APC is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium we observed development of endogenous Th cells with restoration of Th cell dependent antibody responses and immunity to cytomegalovirus infection, thus opening the posssibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA