THelperCellSurfaceMolecules

T helper cells play an essential role coordinating the activities of other parts of the immune system, including B cells, cytotoxic T cells, macrophages and other cells. The crucial nature of helper T cells in the normal immune response is demonstrated by the severe immune deficiency associated with the HIV-induced helper T cell depletion. To communicate with other cells, helper T cells express a range of cell surface molecules, a few of which are illustrated in this figure. Like all T cells, helper T cells express T cell receptors complexed with the CD3 proteins that are responsible for the recognition and response of the cell to specific antigens (see “T Cell Receptor Signaling Pathway”). CD4 is commonly used as a marker for helper T cells, in contrast to cytotoxic T cells, which express CD8. CD4 is used by HIV to gain cell entry, as well as the CCR5 chemokine receptor. Thy1 provides a more general cell surface antigen used to identify both T helper and cytotoxic T cells. CD28 provides a costimulatory signal in association with the activation of the T cell receptor complex by an antigen presenting cell that is required for the T cell to become activated (see “The Co-Stimulatory Signal During T-cell Activation” pathway). Adhesion molecules on the surface of T cells assist in their interaction with other cells. LFA-1 binds to its ligand ICAM-1 in a variety of cells and T cells themselves also express ICAM-1. The CD45 protein tyrosine phosphatase dephosphorylates factors in the pathways involved in B cells and T cells activation. Although CD45 is required for T cell receptor activation, exclusion of CD45 from the local membrane region near the T cell receptor appears important for efficient T cell activation. Helper T cells can be subdivided further into Th1 and Th2 cells, distinguished by their response to different antigens, differing cytokine expression and expression of different chemokine receptors (see “Selective expression of chemokine receptors during T-cell polarization”) CD2 is required for efficient helper T cell maturation and stimulates their differentiation, but does not select for a specific increase in Th1 or Th2 populations of cells.

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REFERENCES: Desai DM, Sap J, Silvennoinen O, Schlessinger J, Weiss A. The catalytic activity of the CD45 membrane-proximal phosphatase domain is required for TCR signaling and regulation. EMBO J 1994 Sep 1;13(17):4002-10 He X, Woodford-Thomas TA, Johnson KG, Shah DD, Thomas ML. Targeting of CD45 protein tyrosine phosphatase activity to lipid microdomains on the T cell surface inhibits TCR signaling. Eur J Immunol 2002 Sep;32(9):2578-87 Sasada T, Yang H, Reinherz EL. CD2 facilitates differentiation of CD4 Th cells without affecting Th1/Th2 polarization. J Immunol 2002 Feb 1;168(3):1113-22