Search PubMed⌕ Search

Biomedical subjects

P Toivanen

Publications and source records attributed to P Toivanen.

At least 163 records · Page 9Linked to original sources
PubMed1989

Immunological and bacteriological aspects of reactive arthritis.

It is apparent that in the development of reactive arthritis the patient fails in his first line of defence against the invading microorganism. This results in persistence of the microorganism probably in or close to the intestinal epithelium. Microbial antigens may appear also in the circulation, perhaps as part of the immune complexes, or within cellular elements. Through these transportation mechanisms they enter the synovium, triggering an inflammatory process that leads to reactive arthritis.

Antibodies, Bacterial↗
PubMed1989

Ontogeny of alloreactivity in the chicken as measured by mixed lymphocyte reaction.

Ontogeny of alloreactivity in the chicken thymus and spleen was studied in mixed lymphocyte cultures. Mixed lymphocyte reaction (MLR) to total major histocompatibility complex (MHC) (B-complex in chicken) disparity was first detected in the thymus of 16-day-old embryo and regularly detectable from the 18th embryonal day on. Small strain-specific differences in the strength and appearance of the response were, however, observed. MLR to class I MHC (B-F) antigen disparity was not detectable before hatching. Exogenous interleukin-2-containing supernatant added to the cultures had only a minor effect on MLR of embryonal thymocytes. In the spleen, MLR was first detectable in some strain combinations on day 3 and regularly found on the 7th day posthatching, indicating colonization of peripheral lymphoid organs by thymus-derived mature T cells. Our results show the association of phenotypic and functional maturation of chicken T cells. The ontogeny of alloreactivity can now be compared to the appearance of T cell receptor (TCR), CD4, and CD8-bearing cells in the thymus and peripheral lymphoid organs.

Animals↗
PubMed1989

B-cell differentiation in the chicken: expression of immunoglobulin genes in the bursal and peripheral lymphocytes.

We have studied the expression of immunoglobulin genes in the chicken B-cell precursors, and of a B-cell surface marker (Bu-1) on the bursal and peripheral B cells during normal ontogeny. Since there is no way of distinguishing the precursor cells from the more mature bursal lymphocytes on the basis of surface markers, we chose to study the total bursal lymphocyte population at ages when the numbers of the various precursor cells (bursal, early post-bursal, and post-bursal stem cells) in the bursa are estimated to be at their highest. Thereafter, comparisons with the more mature lymphocytes in the peripheral organs were made. As a result, levels of the lambda and mu transcripts and expression of Bu-1 antigen in the chicken B-cell precursors were found to be unchanged during the post-hatching period. In the light of these experiments, the later events of B-cell differentiation, i.e. the development from the bursal to post-bursal B lymphocytes, occurs without the lambda, mu, and Bu-1 gene loci involved. On the other hand, the higher level of lambda and mu expression in the splenic B lymphocytes indicates that the post-bursal stem cells mature into highly active plasma cells after seeding to the peripheral organs.

Animals↗
PubMed1989

B cell-induced tolerance to class II MHC antigens in the chicken.

Transplantation of cells from the bursa of Fabricius reconstitutes the B cell system of chemically bursectomized chickens. Even allogeneic bursa cells can restore the recipient's B cell system and induce tolerance to donor major histocompatibility complex antigens, but the chimeras cannot mount a T-dependent antibody response. In order to study the mechanisms of tolerance to class II MHC (B-L) antigens, we transplanted class II-incompatible bursa cells from 4-day-old donors into cyclophosphamide-treated recipients of the same age. Donor and host cells carried different allelic products of a genetically polymorphic B cell alloantigen (Bu-1), allowing us to detect cellular chimerism using monoclonal antibodies and immunofluorescence. The B cell-chimeric chickens were tested for tolerance by skin grafting, graft-versus-host splenomegaly assay, and mixed lymphocyte reaction. Specific unresponsiveness to donor MHC antigens was observed in all three tests. When spleen cells from chickens tolerant of donor class II antigens were transferred into irradiated secondary recipients of the same strain, several of the secondary recipients accepted primary donor-type skin grafts. Most secondary recipients were, however, reactive in the GVH assay and MLR. Depletion of chimeric B cells before spleen cell transfer impaired the transferability of tolerance to class II disparity. Altogether, our results indicate that tolerance to class II antigens can be induced with B cells. They suggest that at least two different mechanisms maintain the unresponsiveness in B cell-chimeric chickens.

Animals↗
PubMed1988

Antigen-presenting cell-T cell interaction in the chicken is MHC class II antigen restricted.

The involvement of the MHC in the recognition of Ag by avian T lymphocytes was analyzed. PBL from chickens primed with keyhole limpet hemocyanin in vivo were induced to synthesize DNA in an in vitro response to specific Ag. Responding cells were T cells as judged by immunofluorescence staining. In vivo Ag-primed PBL were stimulated in vitro with specific Ag and further propagated in the presence of IL-2. Subsequent Ag-specific T cell proliferation required the presence of Ag-pulsed peripheral blood adherent cells (APC). T cell responses were restricted by the MHC of the APC; Ag presented by allogeneic APC did not support T cell proliferation. By using MHC-recombinant chicken lines, the gene products controlled by MHC class II loci were shown to restrict the T cell-APC interaction. This conclusion was substantiated by the inhibition of the Ag-specific T cell response by a mAb against chicken MHC class II gene products but not by a mAb against chicken MHC class I gene products.

Animals↗
PubMed1988

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↗
PubMed1988

Antibody-forming capacity of B cell-deficient chickens reconstituted with limiting numbers of B cell precursors.

To examine the antibody-forming capacity of neonatally cyclophosphamide-treated chickens reconstituted with limiting numbers of B cell precursors, we analyzed their antibody responses to six unrelated antigens. Our results demonstrate that about 10 x 10(6) bursal cells are needed in this adoptive cell transfer model to restore normal immune competence to B cell-deficient birds. From our earlier data we know that with low repopulating cell numbers (less than 10 x 10(6) cells) developing bursal follicles are of clonal origin. Ten million cells repopulate about 40%, i.e. about 4 x 10(3) of the bursal lymphoid follicles. Assuming the clonal origin of the follicles these results imply that the B cell system of birds receiving this dose is derived from less than 5 x 10(3) precursor cells. At the lowest reconstituting dose (1.25 x 10(6) cells) most birds do not respond to the antigens studied. However, their B cell system is derived from only about 500 precursor cells. Because the antibody repertoire of a normal chicken was estimated to be at least 10(6) our results suggest that each precursor gives rise to a large number (greater than 200) of immunoglobulin V-region gene variants during its clonal proliferation in the bursa. Our results are thus consistent with the proposed "hyperconversion" mechanism of generation of antibody diversity in the chicken and provide quantitative data useful for estimating what such somatic modification rates might be.

Animals↗
PubMed1988

Monoclonal antibodies against chicken Bu-1a and Bu-1b alloantigens.

The production and characterization of monoclonal antibodies (mAbs) against chicken B cell surface alloantigens, Bu-1a and Bu-1b, is described. Flow cytometric analysis using these mAbs demonstrates that Bu-1 gene locus does not show allelic exclusion. Two color fluorescence analysis using simultaneous surface marker labeling and DNA staining shows that the expression of Bu-1 antigen is not restricted to a specific phase of the cell cycle. Earlier findings that Bu-1 locus is not linked to the MHC locus are confirmed. Furthermore, data is presented that Bu-1 antigen expression is not entirely B cell restricted. Apparently a fraction of larger mononuclear cells with typical light scatter characteristics in flow cytometry also bear this marker. MAbs against both allelic Bu-1 antigens are beneficial tools e.g. in typing of chicken lines and in studies on chicken B cell differentiation.

Animals↗
PubMed1988

Experimental Yersinia-associated arthritis in the spontaneously hypertensive rat.

Sterile arthritis resembling human reactive arthritis was induced in spontaneously hypertensive SHR rats by intravenous injection of live Yersinia enterocolitica 0:8. Histologically the synovitis appears as proliferation of the lining cell layer, with inflammatory cells present in the subsynovium. The inflammatory cells are mostly lymphocytes. Infection with Yersinia enterocolitica 0:3 or Yersinia pseudotuberculosis did not induce arthritis. Susceptibility to Yersinia-associated arthritis is not determined by the major histocompatibility complex (MHC), since rats of the normotensive control strain (WKY) with the same MHC do not develop arthritis.

Animals↗
PubMed1988

Susceptibility to tolerance induction of bursal and peripheral B cells.

We investigated cellular aspects of immunological tolerance to protein antigens in chickens by examining the immune responses of bursal and splenic cells from tolerant or normal chickens after transfer into cyclophosphamide (CP)-treated recipients. Newly-hatched chicks were made tolerant to bovine serum albumin (BSA) by injection of 100 mg of the antigen. When bursa cells from 4-day-old BSA-unresponsive chicks were transferred into CP-treated recipients, the reconstituted birds were able to respond to a subsequent injection of BSA almost as well as normal birds, and as well as CP-treated birds that had been reconstituted with normal bursa cells. To investigate whether the presence of the BSA antigen might affect recovery from tolerance, we injected CP-treated recipients with BSA at the time of transfer of bursal cells. The presence of the antigen prevented the recovery of the anti-BSA response in reconstituted birds. When spleen cells from 6.5-week-old unresponsive chicks were transferred into CP-treated recipients, no recovery of responsiveness to BSA could be demonstrated. A likely reason for the failure of splenic B cells to recover responsiveness on transfer is their inability to generate somatic variants of Ig genes in the same way as bursal stem cells. Thus, when the bursa involutes, the chicken's antibody repertoire may be frozen in a less adaptable state than that of a mammal.

Animals↗
PubMed1987

Granulocyte-specific monoclonal antibody inhibiting cytotoxicity reactions in the chicken.

Monoclonal antibody (MAb) 1C3, specific for chicken granulocytes, is described for the first time. Treatment of peripheral blood leukocytes with this MAb markedly decreased natural cytotoxicity reaction against the target cell line. The antibody-dependent cellular cytotoxicity (ADCC) activity of purified granulocytes was also severely affected by treatment with MAb 1C3. These results suggest that 1C3 detects a functional surface antigen on chicken granulocytes and support the hypothesis that granulocytes are the main effector cells in natural cytotoxicity in the chicken.

Animals↗
PubMed1987

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↗