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Org by HINARI on 08/29/07. For personal use only. addition to integrin type. In contrast to LFA-1on lymphocytes which is regulated by activation, LFA-I expressed in COScells is constitutively active, and avidity was not further increased by phorbol ester treatment (169). Similarly, VLA-5(fibronectin receptor) is constitutively active nonmitotic fibroblasts, but when expressed on resting T lymphocytes, VLA-5and VLA-6have low constitutive avidity for fibronectin and laminin, respectively, which can be increased by treatment with phorbol esters or TCRcross-linking (63).

Alternatively, distinct regulation of LFA-1on antigen-presenting cells may have a profound effect on the kinetics of interaction with helper T lymphocytes. In fact, the avidity of LFA-1 on B lymphocytes, a major antigen presenting cell type, is increased by ligation of MHC class-II antigens (see Figure I B) (157). The kinetics of the LFA-1 avidity increase that is stimulated by TCRcross-linking are consistent with the kinetics of active CTLinteraction with target cells (4). The TCR-stimulated increase in LFA-1avidity is blocked by increasing cytoplasmic cyclicAMPor by inhibiting protein kinase C.

Annual Reviews LYMPHOCYTEADHESION AND LOCOMOTION 88~8 ~s 35 Annual Reviews 36 DUSTIN & SPRINGER 66), may contribute to the relatively intact lymphocyte migration in LADpatients. Integrin function appears to be required for invasion of the thymus by thymocyte progenitors during early development (67). novel lymphocyte fl subunit has been found to associate with ~4 to form LPAM-2(~4flP), a receptor for Peyer’s patch endothelial cells (68). In addition, in vitro activation of lymphocytes over a period of weeks results in expression of the very late activation antigens el//1, ~2fll, and a molecule similar or identical to eVil3 (56, 69).

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Annual Review of Immunology Volume 9 1991 by Annual Reviews

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