【正文】 stimulatory molecules, and cause intracellular signaling, resulting in activation of the lymphocyte and production of cytokines. Figure 161 Lineage relationships of maturing T cells. γδTcell receptor (TCR) and αβTCR–expressing cells are separate lineages that develop from a mon precursor. In the αβ lineage, the majority of thymocytes express both CD4 and CD8. TCR expression mences in this doublepositive stage, beginning with low numbers of receptors on each cell and increasing as maturation proceeds. Singlepositive (., CD4 or CD8 αβTCR–expressing mature cells) are selected from this population. Some αβ cells express CD4 or CD8. 12 TLymphocyte Activation Tcell activation is an elegant series of events that are still in the process of full delineation ( Fig. 16–2 ). Antigen recognition by T cells is the initiating stimulus for their activation, proliferation, cytokine production, and performance of regulatory or cytolytic effector functions. The TCR is posed of membrane proteins expressed only on T lymphocytes. The TCR does not recognize soluble antigens。 TCR, Tcell receptor. THE CELLS INVOLVED IN ALLOREACTIVITY The key ponents of the immune system—T cells, B cells, and APCs—are produced by the hematopoietic stem cell. As the fetus matures, the bone marrow bees the primary site for lymphopoiesis. The pre–T cells migrate to the thymus, which bees the primary lymphoid an wherein CD3+ T lymphocytes mature and bee ―educated‖ to self. The mature T cells are then released to populate the peripheral lymphoid tissues, including lymph nodes, spleen, and gut. Another lymphocyte subpopulation produced by the hematopoietic stem cell is the B cell. B cells derive their name from the primary lymphoid an that produces B cells in 8 birds, the bursa of Fabricius. In the human and other mammals, the bone marrow is the primary site of Bcell development. The T cells, B cells, and APCs have unique roles in orchestrating the immune response. It is a very tightly controlled work, with most munication mediated by cytokines. B cells have the unique capacity to synthesize antibody. A behavioral difference between B and T cells reflects their functional abilities. When an an is transplanted, responsive clones of T cells are activated in the an itself. In addition, donor dendritic cells leave the graft, home to host lymph nodes, and stimulate both host T cells and B cells therein. Activated T cells leave the lymph nodes and can augment the cellular response in the graft. B cells send out antibody molecules that bind to antigens in the graft within a few days, mediating destructive reactions. Considerable progress has been made in dissecting the mechanisms of Tcell maturation in the thymus. Precursor T cells migrate to the thymus where they undergo maturational changes. All T cells express on their surface an antigenspecific TCR, which is the site for antigen binding. The majority of T cells are αβTCR+ . A smaller subpopulation, which primarily resides in the gut, is γδTCR+ . There are also transmembrane proteins (CD3) with the TCR. Collectively, these plexes pose the TCR plex and provide the signaling molecules needed to respond to foreign antigens. 9 The thymic stromal cells produce two types of molecules that are important for Tcell maturation. The first type is thymic hormones (., thymopoietin and thymosin) and the cytokine interleukin7 (IL7), which regulate the functional differentiation of the peripheral Tcell system. The second type is MHC molecules that are important for selection of the Tcell repertoire. Fundamental properties of a mature Tcell repertoire include (1) restriction to selfMHC and (2) tolerance to selfantigens. The development of selftolerance occurs through both central and peripheral mechanisms. Each of these mechanisms is vital for the discrimination of self/nonself. Central tolerance is achieved through clonal deletion occurring in the thymus. The acquisition of the TCR plex takes place through a series of geically programmed maturational steps. Pre–T cells, not expressing CD4 or CD8 molecules, enter the thymus and proliferate to an intermediate stage of development where they bee double positive (CD4+ and CD8+ ) cells. These cells are educated by selfMHC class I or class II (present on host stromal cells). T cells expressing TCR molecules that interact at an intermediate affinity with selfMHC survive whereas those with too low or too high affinities for MHC do not. This phenomenon is termed positive selection. Cells that do not bind to class I or class II undergo programmed cell death or death by neglect. After positive selection occurs, the developing T cells are exposed to selfantigens. If they react too strongly to selfantigen MHC plexes, they are deleted from the immune repertoire, a phenomenon termed negative selection ( Fig. 16–1 ). 10 Programmed Cell Death Not all progeny of stimulated T cells proliferate but instead die by a process called apoptosis. Apoptosis is a form of regulated cell death. This programmed cell death is an important homeostatic mechanism that limits the lymphoid pool, allowing it to remain relatively constant throughout a lifetime. Activationinduced cell death (AICD) is an apoptotic pathway that is important in the maintenance of selftolerance in the periphery. The hallmark of this system is Fas(CD95)/FasL(CD95 ligand) interactions. The physiologic importance of this system is to prevent uncontrolled Tcell activation and resulting autoimmune disease. Fas is a surface receptor expressed on activated T cells. The expression of FasL occurs in response to increased levels of IL2 secreted by activated T cells. This expression of Fas and FasL leads to cell death through apoptosis. The Fas/FasL system is believed to be one mechanism to control immune respons