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Chemokines have been convincingly implicated in driving leukocyte emigration in different inflammatory reactions. However, the cellular and molecular mechanisms of chemokine involvement in leukocyte emigration are not clear. We and others suggested that leukocyte adhesion to the endothelium and transmigration are induced by chemokines immobilized on the endothelial cell surface. This would require the presence of specific chemokine binding sites in this microanatomical location. Using an in situ binding assay we demonstrated the presence of binding sites for interleukin-8 (IL-8) and RANTES, but not monocyte inflammatory protein-1 alpha on the endothelium of postcapillary venules and small veins in human skin. In contrast, venules and veins in various anatomical locations showed dramatically differing IL-8 binding patterns. The subcellular distribution of IL-8 in the venular endothelial cells following its in vivo and ex vivo injections was studied by use of electron microscopy. Our results suggest that IL-8 was internalized by the endothelial cells, transported transcellularly via plasmalemmal vesicles, and released onto the luminal surface where it appeared located preferentially on tips of membrane protrusions. We were unable to study the endothelial IL-8 binding or transport in vitro because all the in vitro propagated endothelial cell lines and primary endothelial cells tested lacked IL-8 binding sites. This includes human umbilical vein endothelial cells (HUVECs), which also did not bind IL-8 in situ. However, HUVECs provided a satisfactory in vitro system to study the secretion of IL-8 by the endothelial cells. Two possible alternative pathways were described: secretion directly from the Golgi apparatus or following storage in Weibel-Palade bodies.

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The IgG isotype profile of the influenza virus-specific immune response was studied by quantitation of serum antibody (Ab) levels in correlation with the enumeration of antibody-secreting cells (ASC) detected in the lung, spleen, mediastinal lymph nodes (MLN), Peyer's patches and bone marrow (BM). Distinct isotypic patterns for serum Ab and Ab produced by cells present at or close to the site of infection were found after primary or repeated infections. An elevated number of IgM ASC was found after primary challenge in the spleen, lung and MLN. In contrast, the site of IgA and IgG production is restricted to the lung and lymph nodes draining the site of infection. In these organs IgA, IgG2a and IgG1 ASC are found as a result of primary virus infection while viral challenge induces mostly activation of IgA-producing cells and secretion of IgA to the lung lavage. In contrast, the majority (80-90%) of Ab detected in the serum belong to the IgG2a subclass and their serum level is maintained at a high level during the whole period of the response. The relative level of virus-specific serum IgG2a in correlation with the production of IgG2a Ab found predominantly in MLN and lung is highly dependent on the viral dose used for priming or challenge. As IgG2a ASC can be detected at relatively low numbers in the spleen and BM these results suggest that the production of the dominant IgG2a isotype of serum Ab occurs close to the viral challenge site. These data, however, point to distinct isotypic regulation in systemic versus local virus-specific Ab responses.

Abstract. To determine the tissue localization of lymphocytes provisionally termed "complement-receptor lymphocytes," which are characterized by having a membrane receptor for antigen-antibody-complement complexes, we investigated the adherence of sensitized and nonsensitized sheep red cells to frozen sections of mouse lymphoid organs. Nonsensitized erythrocytes became bound exclusively to sinus-lining cells of spleen and lymph nodes, whereas erythrocytes sensitized with antibody and complement adhered to lymphocytes in the follicular areas and the marginal zone of the spleen and in the true cortex of lymph nodes. However, the doubly sensitized erythrocytes failed to bind to the "thymus-dependent" areas of peripheral lymphoid organs or to the thymus itself. We suggest that complement-receptor lymphocytes are of extrathymic origin and that they contribute substantially to follicular antigen localization, which appears to be complement-dependent.Certain immune responses seem to depend on the cooperation of thymusderived and non-thymus-derived lymphocytes.1-4 In studies of the interaction between these cell lines it may be desirable to make use of morphologic or functional markers unique to either one of the two subpopulations.In lymphocyte suspensions from different mammalian species, including man, a proportion of cells were regularly found6 6 to react with sheep erythrocytes (E) which had been sensitized with antibody (A) and complement (C). The adherence of these sensitized erythrocytes (EAC) to such lymphocytes-provisionally termed "complement-receptor lymphocytes" (CRL)-results in the formation of characteristic rosettes (Fig. 1). The complement component required for this interaction was tentatively identified as C3.7 While similar rosettes were also formed with other leukocytes,' 6'8 adherence of EAC to macrophages and polymorphs was shown to require divalent cations and to be blocked by EDTA.5 6 9 In contrast, EAC-reactivity of CRL could not be abolished by EDTA.As compared with lymphocytes that lack the ability to bind EAC (non-CRL), CRL from mouse lymphoid tissues showed an increased adherence to nylon wool and accumulated in the lighter bands of an albumin density gradient.7 Moreover, most of CRL were found to bear immunoglobulin determinants on their surface.7 991

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