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Biomedical subjects

O Lassila

Publications and source records attributed to O Lassila.

At least 19 recordsLinked to original sources
PubMed1995

Primed avian gamma delta T cells respond to mycobacterial antigens, but show no preference for the 65-kDa heat shock protein.

We have studied the reactivity of chicken T cells to mycobacterial antigens. Neither peripheral blood nor splenic lymphocytes isolated from unprimed chickens proliferated in response to mycobacterial antigens (mycobacterial sonicate, purified protein derivative, or recombinant 65-kDa heat-shock protein HSP65). After immunization with complete Freund's adjuvant (CFA) a strong response appeared, and a transient increase of peripheral blood gamma delta T cells was observed. Analysis of spleen cells isolated from CFA-primed chickens showed that both alpha beta and gamma delta T cells were activated by the mycobacterial antigens, apparently at equal levels. Both subsets also responded to HSP65, but no preference of gamma delta T cells to respond to it or any of the other mycobacterial antigens was observed. These results indicate that although HSP65 is an important mycobacterial antigen, it is not dominant in the chicken gamma delta T cell repertoire. Moreover, the results show a clear distinction between the naive and primed repertoire of gamma delta T cells.

Animals↗
PubMed1995

Intraembryonic haemopoietic cells and early T cell development.

T cell precursors in the chick embryo have been localized into the intraembryonic mesenchyme (IEM) and into the para-aortic region before the first wave of the thymic colonization on embryonic day (ED) 6,5-8. The cell surface markers of avian prethymic stem cells are not known. It is also not known whether these precursor cells are already committed to the T cell lineage before their thymic colonization. In 7-day-old chick embryos Ov+ cells were found in the para-aortic region. Also the endothelial cells of the embryonic dorsal aorta were positively stained. Ov antigen might represent a very primitive marker for precursor cells having the potentiality to differentiate both to haemopoietic and endothelial cells. Scattered CD45+ cells were observed in the same para-aortic area as in many haemopoietic areas in the loose embryonic mesenchymal tissues. CD8 alpha (MoAb 3-298) expressing haemopoietic cells were detected before thymic colonization on ED6. In flow cytometric analysis of IEM precursors Ov, CD45 and CD8 alpha expressing cells seemed to form distinct subsets suggesting heterogeneity of these haemopoietic cells.

Animals↗
PubMed1994

Association of HLA antigens with anti-Scl-70-antibodies and clinical manifestations of systemic sclerosis (scleroderma)

Thirty patients with systemic sclerosis (scleroderma) and 188 healthy controls were studied for class I and class II MHC antigens. All patients with scleroderma fulfilled the ARA preliminary criteria for systemic sclerosis. The frequencies of HLA antigens B8, DR3 and DR52 were higher in patients with scleroderma as compared with controls. Ten patients had anti-Scl-70 antibodies, and four of them (40%) had HLA-DR5 antigen compared to 19 of 188 controls (10%), P = 0.013. The relative risk for DR5 in anti-Scl-70-positive patients was 3.6 compared to 1.6 of DQ3 suggesting the primary significance of DR5 compared to DQ related factors. Patients with neurological manifestations had higher frequencies of B8 and DR3 than those with no neurological manifestations of scleroderma. Our results support the view that immunogenetic background is associated with different clinical subsets of systemic sclerosis.

Adult↗
PubMed1994

Intra-embryonic haemopoietic cells and early MHC expression.

In the avian embryo the haemopoietic stem cells originate from the intra-embryonic area near dorsal aorta. The surface-marker expression of haemopoietic stem cells and their potential to produce different haemopoietic cells are still largely unknown. The surface antigen expression and particularly the MHC antigen expression on intra-embryonic haemopoietic cells was studied. Expression of B-F antigens, homologous to mammalian MHC class-I antigens, was found already on embryonic day (ED) 5. The first B-L antigens, analogous to mammalian MHC class-II antigens, were detected also from ED5 onwards. The appearance of surface antigens defined by MoAbs T10A6 and 3-298 during embryogenesis also was studied. The antigen defined with T10A6 was detected from ED4 onwards on endothelial cells but not on haemopoietic cells in the para-aortic region. The first 3-298+ haemopoietic cells were found on ED6, whereas endothelial cells were negative. These findings imply that some surface markers are shared with haemopoietic and endothelial cells indicating either a common embryonic origin or the importance of these molecules in embryonic stem-cell homing.

Animals↗
PubMed1994

Gamma delta and alpha beta T cells are equally susceptible to apoptosis.

Little is known about the role of apoptosis in the regulation of gamma delta T cell development and function. We have used chicken as a model to study apoptosis of gamma delta T cells at different stages of their development. Apoptosis was measured with electrophoretic analysis of DNA fragmentation and flow cytometric determination of DNA content combined with immunofluorescence staining of cell surface molecules. In vitro culture, dexamethasone, and gamma-irradiation induced apoptosis of both gamma delta TCR+ thymocytes and peripheral gamma delta T cells. Apoptosis could be induced even in the earliest thymic gamma delta thymocytes on embryonic day 13. Resting peripheral blood gamma delta T cells were more resistant to apoptosis than thymocytes and spleen cells. Following polyclonal activation of splenic gamma delta T cells by Con A, the proportion of the CD8+ gamma delta T cell blasts decreased significantly when recultured without further stimulation. These results indicate that gamma delta T cells are susceptible to apoptosis in a manner similar to alpha beta T cells, and suggest that apoptosis plays an important role in the regulation of the development and function of both thymic and peripheral gamma delta T cells.

Animals↗
PubMed1994

Evolutionarily conserved function of CD28 in alpha beta T cell activation.

The functional role of the chicken homologue of CD28 was studied. It is expressed on all thymocytes, and both V beta 1- and V beta 2-family expressing peripheral alpha beta T cells. Peripheral gamma delta T cells are CD28-negative. Monoclonal antibody against CD28 had a costimulatory effect on T cells stimulated by phorbol myristate acetate (PMA), concanavalin A or MoAb against TCR. V beta 1 and V beta 2 expressing cells responded equally well to stimulation with anti-CD28 in combination with PMA. These responses were resistant to cyclosporin A, but inhibited by herbimycin A, suggesting that CD28 employs a signalling pathway at least partly distinct from that triggered by TCR/CD3. These data indicate a striking conservation of the costimulatory function of CD28 and emphasize the importance of this costimulatory pathway.

Animals↗
PubMed1994

Association of anti-U1RNP- and anti-Scl-70-antibodies with neurological manifestations in systemic sclerosis (scleroderma).

Thirty-one patients with SSc were studied. Eleven patients had anti-Scl-70-, six had anti-U1RNP-, three had anticentromere antibodies, and one both anti-Scl-70- and anticentromere antibodies. Eleven patients (35%) had neurological findings (trigeminal neuropathy, polyneuropathy, in some with myopathy). Eight of these patients (73%) had either anti-U1RNP- or anti-Scl-70-antibodies in their serum. These findings suggest that neurological manifestations are not as uncommon in SSc as previously reported. There are probably subgroups of patients who are more prone to neurological manifestations of scleroderma (mostly patients with anti-U1RNP and possibly those with anti-Scl-70 antibodies).

Adult↗
PubMed1994

Central role of CD4+ T cells in avian immune response.

Chicken alpha beta T cells express either CD4 or CD8 accessory molecules, whereas most of the gamma delta T cells do not. The functional significance of the alpha beta T cells is relatively well understood. The CD4+ alpha beta T cells function as coordinators of the immune response, and CD8+ alpha beta T cells are the effector cells in cytotoxic responses, killing infected target cells. In comparison, the role of gamma delta T cells is so far poorly known. In chicken, the gamma delta T cells comprise a large lymphocyte subset. They can be induced to proliferate by various stimuli, but the proliferative response is dependent on CD4+ alpha beta T cells. The CD4+ T cells are also essential for the generation of antibody responses by providing help for the B cells and can influence cytotoxic responses as well. Thus, the CD4+ alpha beta T cells have a central role in the avian immune system, and their activation is a prerequisite for responses by other types of cells, including gamma delta T cells.

Animals↗
PubMed1994

[Superantigens].

Explore the source record for details and available documents.

Humans↗
PubMed1993

Androgen-induced expression of the peripheral blood gamma delta T cell population in the chicken.

Unlike alpha beta T cells, the physiologic significance of gamma delta T cells has remained elusive. In avian species they comprise a large circulating T cell subset. Here we report that in chicken around the time of sexual maturation (4 to 6 mo of age) a significant increase of the gamma delta T cells takes place in male but not in female chickens. The frequency of gamma delta T cells increases both in peripheral blood and spleen, but not in intestinal epithelium. This expansion is independent of MHC haplotype, being observed in various inbred and MHC-recombinant strains. Furthermore, administration of testosterone to young female chickens induces an equivalent increase in the frequency of gamma delta T cells in peripheral blood. These results indicate that sex, through androgens, has an effect on the gamma delta T cell numbers in a species, in which these cells form a major subset of peripheral lymphocytes.

Animals↗
PubMed1993

Helper activity of CD4+ alpha beta T cells is required for the avian gamma delta T cell response.

We have studied the in vitro activation of chicken gamma delta T cells. Both splenic alpha beta and gamma delta T cells obtained from complete Freund's adjuvant-primed chickens proliferated in vitro when stimulated with mycobacterial sonicate or purified protein derivative of Mycobacterium tuberculosis. When CD4+ cells or alpha beta T cell receptor (TcR)-positive cells were removed, both the proliferation and the blast formation of gamma delta T cells in response to mycobacterial antigens were abrogated. The response was restored if supernatant from concanavalin A (Con A)-activated lymphocyte cultures (CAS) as a source of helper factors was added together with the specific antigen purified protein derivative. The CD4- or alpha beta TcR-depleted cells still proliferated in response to Con A, although a decrease of the response was observed. To analyze the gamma delta T cell response more specifically we stimulated peripheral blood cells with immobilized monoclonal antibodies against T cell receptor. Anti-gamma delta TcR antibody alone did not induce significant proliferation. When CAS was added together with the anti-gamma delta TcR monoclonal antibody, a strong proliferation of gamma delta T cells was observed. In contrast, both V beta 1- and V beta 2-expressing alpha beta T cells proliferated in vitro in response to stimulation with the relevant anti-TcR monoclonal antibody alone. Depletion of either V beta 1+ or V beta 2+ T cell subset alone had no negative effect on the proliferation or blast formation of gamma delta T cells stimulated with mycobacterial antigens. Taken together our results suggest that CD4+ alpha beta T cells (both V beta 1- and V beta 2-expressing) play a role in the activation and response of chicken gamma delta T cells.

Animals↗
PubMed1992

Involvement of the avian mu heavy chain in recolonization of the bursa of Fabricius.

In the chicken, the B cells develop in a specialized organ, the bursa of Fabricius. Earlier it was shown that neonatal bursal cells treated with polyclonal anti-chicken immunoglobulin antibodies are not able to recolonize the bursa when transferred into cyclophosphamide-treated chicks. In this study, 4-day-old bursal cells were treated with different polyclonal and monoclonal anti-immunoglobulin antibodies and transferred into 4-day-old cyclophosphamide-treated chickens. Two monoclonal anti-chicken IgM antibodies, CVI-59.7 and 21-2B2, recognizing distinct epitopes of the mu heavy chain, were inhibitory. Incubation of cells with 21-2B2 antibody caused about 90% inhibition of bursal recolonization. After incubation with CVI-59.7 antibody the inhibition was 50%. The high inhibition by 21-2B2 antibody was also seen when F(ab')2 fragments of the antibody were used. These results suggest that the entry of the cells needed for bursal recolonization is inhibited almost totally by 21-2B2 antibody, or that this antibody blocks further proliferation of the cells in bursal follicles. In conclusion, we have shown that a mu heavy chain epitope is intimately involved in the recolonization of bursal follicles, and distinct epitopes of the mu heavy chain are not equally important in this process.

Animals↗
PubMed1991

Characterization of the putative avian CD2 homologue.

We describe two mouse mAb recognizing the putative chicken homologue of mammalian CD2 Ag and provide evidence for both structural and functional conservation between the avian and mammalian CD2 molecules. The antibodies were T cell-specific and immunoprecipitated a single diffuse band of Mr 40,000 from lysates of surface-labeled chicken thymocytes and peripheral T cells. Removal of N-linked carbohydrate with endo-beta-N-acetylglucosaminidase F revealed the core protein size of Mr 25,000. A rabbit antiserum raised against a synthetic peptide (CD2-300), composed of 18 amino acid residues of the conserved cytoplasmic domain of human, mouse, and rat CD2, precipitated an Ag similar to chicken CD2. Sequential precipitation with CD2-300 antiserum indicated the conservation of an avian and mammalian CD2 epitope. CD2 expression on thymocytes starts at day 11 of embryonic development, and, during subsequent development, thymic gamma delta cells are all CD2+, whereas most peripheral gamma delta-T cells lack CD2. Functional conservation between the chicken and mammalian CD2 molecules was demonstrated by the induction of DNA synthesis in chicken thymocytes and peripheral T cells with the combination of anti-CD2 mAb and PMA.

Animals↗
PubMed1990

Bursectomy of chicken embryos at 60 hours of incubation leads to an oligoclonal B cell compartment and restricted Ig diversity.

Chickens that have been surgically bursectomized at 60 h of embryonic development usually generate Ig producing B cells; however, the bursectomized chickens are incapable of specific antibody responses, even after repeated immunization. In the present work, we analyzed the molecular basis of this immunodeficiency. In the bursectomized chickens, DNA sequencing revealed a repertoire of Ig L and H chains with a low number of different V-J and V-D-J joints, indicating an oligoclonal B cell compartment. In addition, the L and H chains belonging to each B cell clone had similar gene conversion events in the V region. In situ hybridization to Harderian gland tissue sections showed, that B cells of the bursectomized chickens were, however, capable of terminal plasma cell maturation. Thus, in chickens that were lacking the bursal microenvironment, 1) only a few B cell precursors differentiated into mature Ig-producing B cells, 2) low rate of gene conversion resulted in restricted Ig diversity. Regarding the chicken B cell differentiation, the present data support a model that the induction of B cell differentiation is a bursa-independent event, whereas the bursa of Fabricius has a crucial role in the amplification and diversification of the embryonic B cell repertoire.

Amino Acid Sequence↗
PubMed1990

Tissue distribution and appearance in ontogeny of alpha/beta T cell receptor (TCR2) in chicken.

We have performed immunoperoxidase staining on cryostat tissue sections and immunofluorescence analysis on cell suspensions to identify cells expressing the alpha/beta T cell antigen receptor during ontogeny and adult life in chickens. We used the mouse monoclonal antibody, TCR2, which was previously shown to recognize the alpha/beta TCR in chickens. TCR2+ cells were observed in thymic cortex and medulla and in T-dependent areas of spleen, intestine, and cecal tonsils of young adult chickens. Some TCR2+ cells were found in the cortex of bursal follicles and in liver. The first TCR2+ cells appear in thymus on Day 13 of the embryonic life and it is only after hatching that TCR2+ cells begin to migrate to the periphery.

Age Factors↗
PubMed1990

In vitro organ culture of embryonic bursa of Fabricius.

An in vitro method for organ culture of embryonic bursa of Fabricius is presented. It is shown that bursa cells proliferate in in vitro culture as evidenced by [3H]-thymidine incorporation. We assessed the expression of B-cell alloantigen (Bu-la and Bu-lb), class I (B-F) and class II (B-L) antigens of chicken major histocompatibility complex (MHC), and surface immunoglobulin (sIg) on cultured bursa cells using specific monoclonal antibodies (mAb). Cells from 13-day and 14-day embryonic bursae incubated in organ culture for 1 to 2 weeks developed characteristic patterns of surface phenotype observed in adult chicken except for B-F antigen, whose expression was much lower than in vivo. These results indicate that the maturation of bursa cells in organ culture follows the in vivo development, except for the expression of MHC class I antigens. Furthermore, we demonstrate the in vitro repopulation of bursae from cyclophosphamide(cy)-treated chickens by cells from Bu-l antigen disparate normal bursae.

Animals↗