User:JulieAuger/sandbox

Cd1-restricted T cells are part of the unconventional T cell family, they do not recognize foreign antigens, they are stimulated by exposure to CD1+ APCs alone(24-26). Many CD1-restricted T cells are autoreactive and are rapidly stimulated to carry out helper and effector functions upon interaction with CD1-expressing antigen-presenting cells. CD1-restricted T cells regulate host defence, antitumor immunity and the balance between tolerance and autoimmunity. CD1-restricted T cells can be divided into 2 functional groups: •	those that produce mainly T helper type 1 (TH1) Cytokines •	those that potently produce both TH1 and TH2 cytokines CD1-restricted T cells can also be divided according to their CD1 molecule. Humans express four CD1 isoforms divided in 2 groups: group 1 CD1 (CD1a, CD1b, and CD1c), group 2 CD1 (CD1d). Group 1 CD1-restricted T cells Group 1 CD1–restricted T cells produce TH1 cytokines and are cytolytic. Many group 1 CD1–restricted T cells are autoreactive. CD1a-autoreactive cells are present at high frequencies in blood and skin. CD1a-restricted autoreactive T cells expressed diverse TCR and produce IL-22, moreover CD1a recognizes skin lipid antigens and is highly expressed on Langerhans cells. This suggest that these T cells play a role in dermal immunity (33, 75). CD1c autoreactive cells has been identified to play a role in tumor detection.2 CD1–restricted T cells can kill immature DCs that are infected 2.	CD1d restricted natural killer T cells or Group 2 CD1-restricted T cells CD1d-restricted NKT cells contribute to host defence by influencing the function of macrophages, Dentritic cells, B cell s and Natural Killer cells. They also contribute to tumor immunosurveillance and can mediate tumor rejection via IL-12 production,Natural Killer or T cell activation, or direct cytolysis CD1d-restricted NKT cells are divided into 2 groups: •	type I NKT cells also called ‘invariant NKT cells’ or ‘iNKT cells’: express an invariant TCRα chain and a limited, but not invariant, range of TCRβ chains. •	Type II NKT cells also called ‘diverse NKT cells’: use αβ TCRs that do not conform to the TCR motifs described above.

Type I NKT cells are less frequent in humans than in mice (1–3% of T cells in most mouse tissues, 50% in mouse liver and bone marrow, and approximately 0.1% of T cells in human blood). After the encounter with the antigen Type I NKT cells rapidly become effector cells (minutes to hours) and produce many cytokines. These T cells also have a cytotoxic activity against CD1d+ tumor targets. Furthermore, type I NKT cells upregulate CD154 and produce many cytokines which activates DCs and increase expression of the costimulatory molecules CD80 and CD86 and produce interleukin 12 (IL-12). This led to a better presentation of antigen to MHC-restricted adaptive T cells, activation of NK cells and enhanced B cell responses. Thus, NKT cells can pro¬mote downstream innate and adaptive immune responses and, in turn, enhance protection against infection and cancer.

Type II NKT cells recognize CD1d but lack the highly conserved TCRα chain and reactivity to α -galactosylceramide (α-GalCer) that classify type I NKT cells. Some type II NKT cells recognize the mammalian glycolipid sulfatide (produced at high concentrations in neuroendocrine tissue) phospholipid antigen lysophosphatidylcholine and some other phospho¬lipid, and lysophospholipid antigens, including phosphati¬dylglycerol, and phosphatidylinositol of microbial and mammalian origin. They can also sense gene products of hepatitis B virus by detecting lysophosphatidylethanolamine generated through the cleavage of phosphatidylethanolamine by virus-induced phospho¬lipases. Even non-lipidic small molecules, such as PPBF (phenyl 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonate), are antigenic for some type II NKT cells. Thus, type II NKT cells seem to recognize diverse antigens presented by CD1d and given that these cells seem to be more abundant than type I NKT cells in humans, it is important to understand their roles and therapeutic potential. CD4- CD1d-restricted T cells cytokines produce mainly TH1. In contrast CD4+ CD1d-restricted T cells produce produce TH1 and TH2 cytokines.