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Lymphocyte recruitment in lymphoid tissues and inflammatory sites occurs in response to two events. The first is adherence of lymphocytes to specialized molecules expressed on the surface of appropriately stimulated vascular endothelial cells known as vascular addressins. The interaction occurs via specialized lymphocyte surface molecules known as homing receptors. There is considerable diversity among these molecules. At least three, and possibly four, different addressin-homing receptor pairs exist, regulating entry into peripheral lymph nodes, gut lymphoid tissue, BALT and intrathoracic lymphoid tissue, and inflamed synovium. Vascular addressins are expressed by specialized endothelial cells known as HEV. HEV are not found in normal lung parenchyma but may be induced to appear during an immune response. The mechanism for induction of HEV is unknown, although it may involve the action of inflammatory cytokines. It is not known whether separate endothelial cells exist with a propensity to develop into HEV or if any endothelial cells will develop into HEV if stimulated in the proper manner. Other accessory, lymphocyte-endothelium adhesion molecule pairs have been described, including LFA-1-ICAM-1 and CD4-HLA-DR. These molecules are induced by exposure of the endothelium to inflammatory cytokines, chiefly IFN-gamma. Thus, local humoral influences present during inflammation can alter the possibility of lymphocyte traffic through the endothelium by regulating the presence of lymphocyte adherence molecules. These processes have been documented to occur in the lung in normal homeostasis (e.g., BALT) and in disease (e.g., immunization with SRBC). After adherence, lymphocytes exit the circulation via amoeboid motility. This motility can be altered and enhanced through chemoattractant substances that act via surface receptors. The biochemical basis of cell motility is not entirely clear but appears to involve a link between the second messengers of receptor signaling and changes in the cytoskeleton, particularly actin filaments and microtubules. Like fibroblasts and smooth muscle cells, lymphocytes appear to respond to a number of "mitoattractants," substances that cause cell cycle entry and/or progression as well as enhanced motility. This relationship illustrates the integral relationship between cell motility and proliferation and suggests that the process of cell recruitment might also prime the recruitment cells to become activated to proliferate and perform effector function. Studies of lymphocyte-mediated lung disease confirm that antigen-specific as well as antigen-nonspecific lymphocytes are selectively recruited to the lung from the circulation during an inflammatory reaction in the lung.(ABSTRACT TRUNCATED AT 400 WORDS)

To detect a potential defect in immunoregulatory function in atopic subjects, we studied histamine-induced suppressor-T-cell activity and histamine Type 1 and Type 2 receptors on T cells. Peripheral-blood mononuclear cells from 16 atopic subjects generated less histamine-induced suppressor activity than did those from 20 nonatopic normal controls (P less than 0.005). The percentage of T lymphocytes bearing histamine Type 2 receptors was lower in the atopic group than in the control group (P less than 0.001), but the percentage of cells with Type 1 receptors was the same in both groups. In the atopic subjects, the functional suppressor-cell abnormality positively correlated with the decreased phenotypic expression of histamine Type 2 receptors. No abnormality in concanavalin A-induced suppressor activity was detected in these subjects. Nonatopic control subjects with systemic mastocytosis had normal functional and phenotypic data, suggesting that chronic activation of atopic T cells in vivo by circulating histamine does not explain the abnormal histamine-induced suppressor response.

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Atherosclerotic lesions contain multiple cell types including smooth muscle cells, macrophages, and T lymphocytes. The development of an extralymphatic T lymphocyte focus of inflammation in this condition requires chemoattractant-induced cell migration and growth factor-induced cell activation. In a previous study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated bovine aortic endothelial cells that is distinct from previously identified endothelial cell-derived interleukins (IL) 1, 6, and 8. Because of the association between T lymphocyte chemotactic and growth factor activity, in the current study we investigated the effect of ED-LCA on T cell growth. We assessed its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR) and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of the p55 subunit of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Passage into the G1 phase of the cell cycle was confirmed by cell cycle analysis employing acridine orange. Evaluation of CD4+ and CD8+ T cell subsets by double-antibody labeling demonstrated that the p55 subunit of IL-2R was induced in both T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce proliferation, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused a proliferative response with a stimulation index of 3. By up-regulating functional cell surface receptors for IL-2, ED-LCA is a competence growth factor for T lymphocytes and primes them to respond to IL-2. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T cell growth factors like IL-2 in the recruitment and amplification of the extralymphatic T cell component of atherosclerosis.

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