Preferred Label : Diabetes mellitus, congenital autoimmune;
Type : Other, mainly phenotypes with suspected mendelian basis;
Description : Jayawardena-Wolf et al. (2001) described 2 different pathways of Cd1d trafficking
to endosomal compartments in mouse cells. A tyrosine-based motif governs recycling
between the plasma membrane and the endosome, while Cd1d associates, like major histocompatibility
complex class II antigens, with the invariant chain, or Ii (CD74; 142790), in the
endoplasmic reticulum. Both pathways enhance antigen presentation to Cd1d-restricted
natural killer T cells. NKT cells express both the alpha-beta T cell receptor and
inhibitory MHC-specific NK receptors (NKR; e.g., LY49, 604274). Unlike autoreactive
T cells, the rare autoreactive NKT cells are not deleted in the thymus but are positively
selected upon recognition of CD1D (with, presumably, an endogenous ligand) expressed
by CD4 CD8 double-positive cortical thymocytes. Deletion of the NKR, or the absence
of MHC molecules on target cells, abolishes control of autoreactivity. Using fluorescent
CD1D tetramers loaded with the synthetic lipid alpha-galactosylceramide, which uniformly
stain all NKT cells expressing the V-alpha-14-J-alpha-18/V-beta-8 TCR, Benlagha et
al. (2002) identified, in 2-week-old mice, predominantly CD44-low NK1.1- thymocytes,
which mature into CD44-high NK1.1- and then CD44-high NK1.1 cells. Other NKR such
as LY49 are also expressed late in NKT cells. Maturation to the NKR stages corresponded
with a conversion from production of TH2- (e.g., IL4, 147780) to TH1- (e.g., IFNG,
147570) type cytokines, with an intermediary phase of mixed IL4/IFNG production. Benlagha
et al. (2002) suggested that the thymic and postthymic developmental pathways expand
autoreactive cells and differentiate them into regulatory cells. In a commentary,
MacDonald (2002) proposed a model for the intrathymic development and export of NKT
cells. Pellicci et al. (2002) used a similar strategy and confirmed the thymus-dependence
of NKT cells by showing that these cells are not produced in athymic nude mice. They
also demonstrated that NKR- cells give rise to NKR cells but not vice versa. CD4
thymocytes may differentiate to either CD4 or CD4- NKR cells. Vincent et al. (2002)
showed that group-1 (i.e., CD1A, CD1B, and CD1C) foreign antigen-nonspecific CD1-restricted
T-cell clones could promote dendritic cell (DC) maturation in the presence of lipopolysaccharide
and;
Prefixed ID : 605026;
Origin ID : 605026;
UMLS CUI : C1857958;
Currated CISMeF NLP mapping
- Semantic type(s)
- UMLS correspondences (same concept)
