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S Jalkanen

Publications and source records attributed to S Jalkanen.

At least 127 records · Page 7Linked to original sources

Expression of B-L and Bu-1 antigens in chickens bursectomized at 60 h of incubation.

Differences in expression between B-L (chicken class II major histocompatibility complex antigen) and Bu-1 B cell antigens were found in normal animals by using monoclonal antibodies and flow cytometric immunofluorescence analysis. Fluorescence intensity profile was used in assaying cell surface density of antigen molecules. The density of B-L antigen on the cell surface is apparently low in immature and high in mature cells, whereas the density of Bu-1 antigen does not vary in cells at different maturational stages. The existence of B-L+ and Bu-1+ cells in chickens bursectomized at 60 h of embryonic development (Bx) is demonstrated, indicating that neither B-L or Bu-1 antigen is exclusively specific for cells differentiated in the bursa. The densities of B-L and Bu-1 molecules on lymphoid cells in Bx chickens are similar to those of controls. However, the number of B-L+ and Bu-1+ cells was decreased in Bx chickens. We conclude that the extrabursal site where Bx B cells mature has an ability similar to that of the bursa to induce and enhance the expression of B-L and Bu-1 antigens. However, only few B cells proliferate and/or are released into the circulation. Further, the extrabursal site unequivocally lacks the most important function of the bursa, the creation and expansion of antibody diversity.

Aging↗

Evolutionary conservation of tissue-specific lymphocyte-endothelial cell recognition mechanisms involved in lymphocyte homing.

Tissue-specific interactions with specialized high endothelial venules (HEV) direct the homing of lymphocytes from the blood into peripheral lymph nodes, mucosal lymphoid organs, and tissue sites of chronic inflammation. These interactions have been demonstrated in all mammalian species examined and thus appear highly conserved. To assess the degree of evolutionary divergence in lymphocyte-HEV recognition mechanisms, we have studied the ability of lymphocytes to interact with HEV across species barriers. By using an in vitro assay of lymphocyte binding to HEV in frozen sections of lymphoid tissues, we confirm that mouse, guinea pig, and human lymphocytes bind to xenogeneic as well as homologous HEV. In addition, we show that mouse and human lymphoid cell lines that bind selectively to either peripheral lymph node or mucosal vessels (Peyer's patches, appendix) in homologous lymphoid tissues exhibit the same organ specificity in binding to xenogeneic HEV. Furthermore, monoclonal antibodies that recognize lymphocyte "homing receptors" and block homologous lymphocyte binding to peripheral lymph node or to mucosal HEV, also inhibit lymphocyte interactions with xenogeneic HEV in a tissue-specific fashion. Similarly, anti-HEV antibodies against organ-specific mouse high endothelial cell "addressins" involved in lymphocyte homing to peripheral lymph node or mucosal lymphoid organs, not only block the adhesion of mouse lymphocytes but also of human lymphocytes to target mouse HEV. The results illustrate a remarkable degree of functional conservation of elements mediating these cell-cell recognition events involved in organ-specific lymphocyte homing.

Animals↗

Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.

The tissue-specific homing of lymphocytes is directed by specialized high endothelial venules (HEV). At least three functionally independent lymphocyte/HEV recognition systems exist, controlling the extravasation of circulating lymphocytes into peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches or appendix), and the synovium of inflamed joints. We report here that antibodies capable of inhibiting human lymphocyte binding to one or more HEV types recognize a common 85-95-kD lymphocyte surface glycoprotein antigen, defined by the non-blocking monoclonal antibody, Hermes-1. We demonstrate that MEL-14, a monoclonal antibody against putative lymph node "homing receptors" in the mouse, functionally inhibits human lymphocyte binding to lymph node HEV but not to mucosal or synovial HEV, and cross-reacts with the 85-95-kD Hermes-1 antigen. Furthermore, we show that Hermes-3, a novel antibody produced by immunization with Hermes-1 antigen isolated from a mucosal HEV-specific cell line, selectively blocks lymphocyte binding to mucosal HEV. Such tissue specificity of inhibition suggests that MEL-14 and Hermes-3 block the function of specific lymphocyte recognition elements for lymph node and mucosal HEV, respectively. Recognition of synovial HEV also involves the 85-95-kD Hermes-1 antigen, in that a polyclonal antiserum produced against the isolated antigen blocks all three classes of lymphocyte-HEV interaction. From these studies, it is likely that the Hermes-1-defined 85-95-kD glycoprotein class either comprises a family of related but functionally independent receptors for HEV, or associates both physically and functionally with such receptors. The findings imply that related molecular mechanisms are involved in several functionally independent cell-cell recognition events that direct lymphocyte traffic.

Antibodies, Monoclonal↗

T cell function in chickens bursectomized at 60 hours of incubation.

Chickens surgically bursectomized in ovo (Bx) at 60 hr of embryonic development offer a unique model to study selectively the influence of the bursa of Fabricius on thymus-dependent immune functions because the lymphoid cells of these animals develop in the total absence of the bursal microenvironment. The Bx chickens have been shown to be unable to respond to antigenic stimulation by specific antibody production. In the present study, we have characterized different aspects of T-cell-mediated immunity in Bx chickens. Our results indicate the existence of a normal, functional T cell system in these animals. Peripheral blood leukocytes from Bx chickens were able to induce normal graft-versus-host reaction and mixed lymphocyte reaction. The capacity of peripheral blood T cells from Bx animals to produce interleukin-2 was indistinguishable from that of their normal counterparts, suggesting normal function of T helper cells. We demonstrate that peripheral blood leukocytes from Bx birds have normal in vitro proliferative responses to nonspecific T cell mitogens, concanavalin A, and phytohemagglutinin, and to a specific antigen, keyhole limpet hemocyanin. The inability of the Bx chickens to respond to specific antigens is therefore restricted to B cells and to production of specific antibodies. Our findings indicate that the bursa of Fabricius is not necessary for the development of thymus-dependent immune functions and support the suggestion that the specific function of the bursa is the creation of antibody diversity.

Animals↗

Human lymphocyte and lymphoma homing receptors.

The migration of normal and malignant lymphocytes is controlled in part by selective lymphocyte recognition of high endothelial venules (HEV) at sites of lymphocyte exit from the blood. Recirculating lymphocytes appear to utilize structurally related, yet functionally distinct, 90-kD receptors to interact in an organ-specific manner with HEV in peripheral lymph nodes, in mucosa-associated lymphoid tissues (Peyer's patches, appendix), and in inflamed joint tissue (synovium). These lymphocyte "homing receptors" constitute a family of glycoprotein endothelial cell recognition elements that regulate the extravasation of circulating normal and neoplastic lymphocytes into different organs of the body, and thus play an important role in determining the characteristics of local immune responses and the patterns of dissemination of lymphoid neoplasms.

Animals↗

Lymphocyte-endothelial cell interactions.

Lymphocyte-high endothelial venule (HEV) cell interaction that is mediated by specific receptors is fundamentally important during normal and malignant lymphocyte traffic. Putative human lymphocyte homing receptors to peripheral lymph node, mucosal (Peyer's patch, appendix) and inflamed joint tissue (synovium) HEV appear to be functionally distinct, but structurally closely related 90 kDa glycoproteins that are highly conserved during evolution. These receptors regulate lymphocyte traffic in an organ-specific manner throughout the body, thus determining the characteristics of local immune responses and possibly also the patterns of dissemination of lymphoid malignancies.

Animals↗

A distinct endothelial cell recognition system that controls lymphocyte traffic into inflamed synovium.

Lymphocytes are essential mediators of normal tissue inflammatory reactions and of pathologic tissue damage in, for example, rheumatoid arthritis and other autoimmune diseases. In a study of the mechanisms controlling lymphocyte entry into sites of inflammation from the blood, the function and specificity of lymphocyte-endothelial interactions were examined in inflamed joint tissue (synovium) from patients with rheumatoid arthritis. Synovial high endothelial venules (HEV) supported the binding of normal peripheral blood lymphocytes in vitro. The characteristics of this binding, which were similar to those of lymphocyte-HEV interactions controlling lymphocyte migration into organized lymphoid tissues, included a requirement for calcium ions, a dependence on metabolic activity, and a preferential adherence of circulating lymphocytes as opposed to immature thymocytes. However, the binding of lymphocytes to synovial HEV was not inhibited by a monoclonal antibody to lymphocyte receptors for lymph node HEV, and synovial HEV failed to bind either lymph node HEV-specific or mucosal HEV-specific B lymphoblastoid cells. The results suggest that a lymphocyte-endothelial cell recognition system that is distinct from such systems in organized lymphoid tissues directs the extravasation of normal lymphocytes as well as pathologically important effector cells into inflamed synovium.

Animals↗

Interactions between endothelial cells and leukocytes.

We present evidence that specific receptors are utilized by neutrophils to control their interaction with endothelial cells at sites of acute inflammation and that these receptors are related if not identical to lymphocyte "homing receptors" for lymphoid tissue high endothelium. We speculate that such receptors play a fundamental but not exclusive role in controlling the extravasation and tissue localization of all bone marrow-derived nucleated cells. In addition, we emphasize the active role of endothelial cells in the process of lymphocyte migration and leukocyte extravasation. By the expression of as yet unidentified organ-specific determinants for lymphocyte recognition, endothelial cells control the exit of particular lymphocyte subsets into mucosal versus nonmucosal sites, thus helping to determine the unique features of mucosal versus nonmucosal immune responses. Furthermore, we argue that endothelial cells are exquisitely responsive to local immune reactivity and present evidence that specific lymphokines, including gamma-interferon, play an important role in inducing postcapillary venules to express differentiated features required for the support of lymphocyte traffic into lymphoid organs and into sites of chronic inflammation. Leukocytes, endothelial cells, and probably other tissue cell classes appear to interact at multiple levels by a variety of mechanisms to regulate the local extravasation of immune effector cells.

Animals↗

Inability to transfer immune unresponsiveness of chickens bursectomized at 60 hours of incubation.

Chickens surgically bursectomized (Bx) at 60 hours of incubation have been found unable to produce specific antibodies, in spite of close-to-normal serum immunoglobulin levels. Suppressor cell overactivity as a reason for the impaired antibody production in the Bx chickens has not been ruled out. In the present work, we have studied whether the state of immune unresponsiveness of the Bx chickens can be transferred to normal chickens by transfer of bone marrow cells. Bone marrow cells from 10-week-old Bx or control (Co) chickens were grafted into x-ray-irradiated histocompatible 5-12-day-old normal recipients. After the transplantation the recipients were immunized with a pool of five antigens, and the antibody responses were quantitated by ELISA. The inability of the Bx chickens to produce specific antibodies could not be transferred to normal chickens by transfer of bone marrow cells, as no differences in the antibody responses between the two recipient groups were observed. The results indicate that suppressor cells do not play a role in preventing specific antibody formation in the Bx chickens.

Animals↗

Homing receptors and the control of lymphocyte migration.

The traffic of lymphocytes is controlled in part by the selective interaction of circulating lymphocytes with specialized high endothelial venule (HEV) cells at sites of lymphocyte exit from the blood. At least three independent receptor systems are responsible for controlling lymphocyte traffic to different lymphoid organs or to sites of inflammation: one mediates lymphocyte interaction with HEV in peripheral lymph nodes, another in mucosa-associated lymphoid tissues, and a third in inflamed synovium. The receptors mediating lymphocyte recognition of HEV in different organs appear to be structurally related yet antigenically and functionally distinct 90 kD glycoproteins. Receptors for lymph node HEV can function as mammalian lectins, and probably interact with specific carbohydrate ligands on high endothelial cells. Mouse and human homing receptors share both antigenic and structural features, indicating a high conservation of lymphocyte-endothelial recognition systems during evolution. They play an essential part in the immune process by controlling lymphocyte traffic during B- and T-cell differentiation, and by segregating effector cells derived from stimulation in different tissues, thus simultaneously increasing the efficiency of organ-specific immune responses and decreasing possibilities for autoimmune crossreactions. Homing receptors are also expressed by many mouse and human lymphoid neoplasms, and appear to play a role in lymphoma metastasis. Related if not identical receptors are expressed by other leukocyte types, including polymorphonuclear leukocytes, monocytes, and large granular lymphocytes (natural killer cells). Thus lymphocyte homing receptors are members of a family of glycoprotein receptors for endothelium that control the extravasation of lymphocytes as well as other leukocytes, and help regulate both non-specific and specific immune responses in vivo.

Animals↗

Immune capacity of the chicken bursectomized at 60 hr of incubation: cytoplasmic immunoglobulins and histological findings.

Chickens were surgically bursectomized at 60 hr of incubation, before the bursal anlage appears. Completeness of the bursectomy was confirmed at autopsy at 10 weeks of age. These embryonically bursectomized (Bx)3 chickens are known to produce immunoglobulins of IgM, IgG, and IgA classes but so far no specific antibodies have been observed even after heavy immunization. The Bx chickens had mature plasma cells in an almost normal frequency when studied at 10 weeks of age. The amount of germinal center formation in the spleen and cecal tonsils was markedly decreased when compared to the control (Co) chickens. Also, the frequency of cytoplasmic IgA-positive (c-IgA+) cells was severely decreased in the Bx animals, whereas the occurrence of c-IgG+ and c-IgM+ cells was not affected to the same extent. These findings support the hypothesis that heavy-chain class switch may occur without the bursal influence, and that the bursa of Fabricius is essential only for expansion or creation of the antibody repertoire.

Aging↗

Immune capacity of the chicken bursectomized at 60 hr of incubation: effect of adherent cells on the production of immunoglobulins and specific antibodies in vitro.

Cells from chickens bursectomized at 60 hr of incubation (Bx) and normal controls (Co) were assessed for the ability to secrete immunoglobulins and specific antibodies in vitro. Anti-tetanus antibodies were observed in the culture supernatants of cells from tetanus-immunized Co chickens. Cells from immunized Bx and nonimmunized Co chickens did not secrete specific antibodies. Cells of both Bx and Co chickens secreted similar amounts of immunoglobulins (IgM, IgG, IgA). Antigenic stimulation in vitro had no effect on the secretion of specific antibodies or on cell proliferation; this applies for Bx and Co chickens. To test whether antigenic stimulation in vitro together with adherent cells would induce antibody production in Bx cells, cocultures of peripheral blood adherent cells and lymphocytes from spleen or peripheral blood were used. Culture of lymphocytes with histocompatible and allogeneic adherent cells, with or without antigenic stimulation, did not enhance secretion of anti-tetanus antibodies from cells of Bx chickens. The adherent cells increased the secretion of total immunoglobulins, of all classes, by both Co and Bx cells alike. They also enhanced the secretion of specific antibodies by Co cells. These findings indicate that the functional failure of Bx lymphoid cells cannot be corrected by better antigenic presentation.

Animals↗

Immune capacity of the chicken bursectomized at 60 H of incubation. Effect of bursal epithelial cells and bursal epithelium-conditioned medium on the production of immunoglobulins and specific antibodies in vitro.

Cells from chickens bursectomized at 60 h of incubation (Bx) are known to produce immunoglobulins without any detectable antibody specificity. In the present work cells from Bx birds were cultured together with bursal epithelial cells (BE) or bursal epithelium-conditioned medium (BECM) to establish whether they could be induced to produce specific antibodies. Cells obtained from 10-day-old or 10-week-old birds were used. The effects were assessed with regard to the production of total immunoglobulins and specific antibodies; the birds had been preimmunized. BE had no effect on the production of immunoglobulins by either Bx or control (Co) cells. When cells from 10-week-old birds were cultured in the presence of BECM, no difference in the immunoglobulin production was seen between Bx and Co chicken cells. At the age of 10 days the cells of Bx birds produced considerably less Ig than the cells of normal Co birds. At this age BECM had no effect on the Co cells, but it markedly enhanced the production of IgA-class immunoglobulins of Bx birds. With regard to production of specific anti-tetanus antibodies, BE stimulated the production of IgA-class antibodies by cells from preimmunized Co chickens but had no effect on cells from preimmunized Bx birds. In spite of the normal production of immunoglobulins in vitro the cells of Bx chickens did not produce specific antibodies. In conclusion, these findings indicate that if B cells have matured without a contact with the bursa of Fabricius, later in vitro exposure to BE or BECM can no longer induce them to production of specific antibodies.

Aging↗