Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 142

(signal 0) and guide the priming of cytotoxic T lymphocytes [ 207 ]. NKT cells
stimulate cognate dendritic cells to produce CCL17 chemokine to recruit effector
CD8 + T cells that possess CCL17 receptor CCR4 [ 263 ].

Invariant Natural Killer T Lymphocytes

Type-1 NKT cells, or invariant NKT cells (iNKT), prime an innate immunity-like
response. They are able to modulate the function of other cell types. In particular,
iNKT cells provoke an effective antitumor immune response [ 264 ].
Invariant NKT cells express a single invariant T-cell receptor α chain (V α 24 -

J α 18 ) that combines with an β chain (V β 11 ), hence the V α 24 + ,V β 11 + phenotype.

This T-cell receptor on V α 24 + ,V β 11 + NKT cells reacts specifically and potently

to CD1d tetramers 133 loaded with the glycosphingolipid antigen α -galactosyl

ceramide on antigen-presenting cells such as CD1d + dendritic cells. V α 24 + ,

V β 11 + NKT cells activate conventional T and NK cells as well as B lymphocytes.

V α 24 + iNKT cells mediate antitumor activity via killing of tumor-associated

macrophages [ 267 ]. 134
Invariant NKT cells also specifically synthesize transcription regulator zinc
finger and BTB domain-containing protein ZBTB16 that is required for maturation
(e.g., secretion of large amounts of interleukin-4 and interferon-

γ after activation)

[ 268 ].
Invariant NKT cells derive from CD4 , double-positive thymocytes.

Transcription factor myeloblastosis viral proto-oncogene product homolog MyB
launches DP thymocytes into the iNKT lineage, as it simultaneously regulates
the expression of CD1d loaded on DP thymocytes, the half-life of DP cells to
allow V α 24 -J α 18 rearrangement, and production of signaling lymphocytic activation
molecule family members SLAMF1 and SLAMF6 and SH2 domain-containing
protein SH2D1a, also called SLAM-associated protein (SAP) [ 269 ].
Mucosal-associated invariant T lymphocytes are similar to CD1d-restricted
NKT cells, but are preferentially located in intestine. Their activation requires
MHC class-1-related protein. Few NKT cells exist in the nasopharynx-associated
lymphoid

+ ,CD8 +

tissue and regional cervical lymph nodes. α -Galactosyl ceramide

133 Cluster of differentiation-1 constitute a family of glycoproteins on the surface of various types
of human antigen-presenting cells. These glycosylated class-1 MHC molecule-like molecules
presents lipid antigens to T cells. The CD1 glycoproteins can be classified into 2 groups according
to their lipid anchoring [ 265 ]. Group-1 CD1 molecules (CD1a-CD1c) are expressed on antigen-
presenting cells. Group-2 CD1 molecules (CD1d) reside on a wider variety of cells. Group-1 and -2
CD1 present both self and microbial lipid antigens to T cells. Group-1 CD1-restricted T cells
recognize mycobacterial glycolipid antigens; group-2 CD1-restricted T cells are regulatory T cells
that act in innate and adaptive immunity [ 266 ]. CD1d-presented antigens activate natural killer
T cells. Intracellular CD1e forms an additional category.
134 CD68

+ tumor-associated monocytes and macrophages represent the majority of CD1d + cells,

at least in some types of cancers. CD68 , tumor-associated monocytes and macrophages produce

IL6 in primary tumors that stimulates tumor growth [ 267 ].

+