T Cells and Brain

The choice of y8 v. ap chains of TCR expression happens at the stage of pre-TCR by selection of cells with productive TCRp rearrangements irrespective of the Vp gene segment used. Rearrangement of TCR generates receptors with different affinity and avidity to an unlimited amount of peptides (derived from self and non-self proteins) in the context of MHC molecules expressed on thymic APC/TEC. 

These mature, but naive T cells exit peripheral blood and seed lymphoid organs in T-cell specific zones to be acquired by adaptive immune responses for elimination of infected or tumor cells, support for humoral immune responses, formation of immunologic memory, prevention of excessive tissue damage, and facilitation of tissue regeneration (see Chapter 12). 

One lineage choice that occurs rather late in T-cell ontogeny is the development of NKT cells. NKT cells express markers of both NK cells and T lymphocytes. These include Ly49 family receptors NKl.l and TCR in mice. Mature NKT cells are CD44 CD69, a phenotype consistent with an activated cell. A hallmark of NKT cells is copious IL-4 and IFN-y secretion promptly upon TCR activation. Because of this property, NKT cells most Likely possess regulatory fimctions. They suppress multiple autoimmune phenomena, and in some cases, inhibit tumor metastases. Unlike conventional a 3 T cells that are selected by classical MHC class I and II, the vast majority of NKT cells are selected by the non-polymoiphic class I-like molecule, CD Id. 

NKT-ceU development is dependent on the protease cathepsin L. As NKT cells react to Lipids, cathepsin L may process a lipid earlier protein that is required for loading lipids onto CD Id. A strong candidate for the lipid carrier protein is prosaposin, a precursor that is cleaved into a series of lipid transfer proteins. As the stmeture of lipids capable of binding CD Id is not as diverse as peptides, it is perhaps not surprising tliat NKT cells exliibit a limited TCR repertoire. The CD Id-restricted NKT cells also differ from mainstream T cells in co-receptor expression. They are CD4 or double negative, and never CD 8 .  

Lymphocyte behavior in brain tissue depends upon functional status of microglial cells, parenchymal and perivascular macrophages. 

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