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O Vainio

Publications and source records attributed to O Vainio.

At least 109 records · Page 6Linked to original sources
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

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↗
PubMed1987

Major histocompatibility complex and cell cooperation.

We have studied the role of major histocompatibility antigens on cell cooperation in the immune response of the chicken. In the 1970's, shortly after the initial discoveries in the mouse, we demonstrated that the T cell-B cell interaction is major histocompatibility complex (MHC)-dependent in the chicken and requires at least one haplotype identity between the collaborating cells. Later, by using MHC-congenic and MHC-recombinant lines, we demonstrated that the T-B cell interaction in antibody response is MHC-restricted, and more precisely, Class II MHC-antigen-restricted. Furthermore, we proved that T-B cell cooperation in splenic germinal center formation is likewise class II MHC antigen-restricted. Recently, we have focused our studies on MHC antigen identity requirements during antigen presentation by macrophages to T cells. In these studies, Class II antigens were found to serve as restriction elements in antigen recognition by T cells. Cytotoxic T cells of the chicken have been shown to be MHC-restricted in their function. Whether Class I or Class II MHC antigens serve as restriction molecules has not yet been determined. In conclusion, it is obvious that the function of the avian immune response is controlled by the polymorphic MHC gene products in the same way as that in the mammalian species.

Animals↗
PubMed1987

A re-evaluation of the function of the bursa of Fabricius.

We will briefly outline mammalian B cell ontogeny to provide a comparison with the avian model. The earliest defined stage of mammalian B cell development is the pre-B cell (itself derived from a multipotent stem cell) which expresses heavy chains within the cytoplasm and is a large, rapidly dividing cell. This cell drops out of division, reduces in size and, over about 24 hours, rearranges Ig light chain V region gene. As a consequence of light chain rearrangement and expression, intact IgM is expressed on the cell surface and the cell leaves the bone marrow as a small virgin B lymphocyte with the capacity to respond to antigen (Opstelten and Osmond 1983). This pathway occurs throughout the life of the animal and so there is constant production of B cells from the bone marrow which are recently derived from sIg- precursors, which have, in turn, recently rearranged their Ig V region genes. Thus there is a constant influx of new V region gene combinations into the peripheral mammalian B cell pool. Furthermore, the mammalian B cell repertoire is very large with estimated germ line diversity approaching 5 X 10(7) as a consequence of various germ-line V region recombinations (Honjo 1983). The pre-bursal stem cell is present in the periphery of the embryo from before day 8 to about day 16 - 17 of embryonation. Most colonisation of bursal follicles probably occurs prior to day 13. Individual bursal follicles are populated by a low number (2-3) of precursor cells. These rapidly become committed for the expression of particular V region genes, probably as a consequence of productive V region recombination. This recombination is restricted to the embryo and may not require the bursal microenvironment for its induction. The available germ-line repertoire of heavy and light chain V region in the chicken is very limited and little diversity can be generated from this initial recombination event (see Weill et al 1986). By day 12 of embryonation, sIg+ cells are present in the bursa and from this time sIg+ cells rapidly divide within the medulla of the bursal follicle. By about day 18 of embryonation, there are no pre-bursal cells in the periphery and sIg+ cells begin to seed from the bursa. It is from about this time that the cortex appears within the bursal follicle and it is tempting to suggest that cells migrate from the medulla to the cortex where further cell division occurs prior to export into the periphery.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Avian B cell precursors: surface immunoglobulin expression is an early, possibly bursa-independent event.

The avian bursa of Fabricius contains about 1 X 10(4) discrete follicles, each of which is colonized by a small number of lymphoid progenitor cells during embryonic life. We have previously shown (J.R.L. Pink et al., Eur. J. Immunol. 1985. 15:617) that all, or almost all B cell progenitors in the bursae of 4-day-old chicks express cell surface IgM. In this report, we have analyzed the distribution of cell surface (s)IgM-1 allotypes within individual follicles of (M-1a/M-1b) allotype heterozygous birds. Although the majority of follicles contained a mixture of sIgM-1a+ and sIgM-1b+ cells, a significant proportion of isolated follicles contained exclusively sIgM-1a+ or sIgM-1b+ cells. Statistical analysis of the frequency of such "M-1a" and "M-1b" follicles demonstrated that the sIg+ B cells in the bursae of 4-8-week-old birds are derived from 2-4 allotypically committed precursor cells per follicle. Since we have previously shown that each bursal follicle is colonized by 2-5 pre-bursal stem cells, these cells must be committed to the eventual expression of one or other allotypic haplotype before they have undergone extensive proliferation within the bursa. In addition, we show that almost all B progenitor cells from the bursae of chicks which had been allotype suppressed as embryos were committed to synthesis of the nonsuppressed allotype, showing that this commitment was essentially complete at the time of suppression (i.e. before 19 days of incubation). Finally the bone marrow of 16-day embryos was used to reconstitute the bursal lymphocytes of cyclophosphamide-treated host embryos. Reconstitution was inhibited by anti-Ig antiserum indicating that most 16-day embryonic BM-derived bursal cell precursors also express sIgM. These results raise the possibility that expression of sIgM may be controlled by a "biological clock" rather than by any inductive capacity of the bursal microenvironment. Furthermore, these results provide further evidence that in normal birds a self-renewing sIg+ B cell population in the hatched chicken is the sole source of B cells in the adult.

Animals↗
PubMed1986

Chicken strain G-B1 exhibits a relative resistance to avian osteopetrosis.

The disease induced by the avian myeloblastosis associated virus MAV-2-O in the susceptible chicken strains Brown Leghorn (BLH) and Prague CB (CB) was compared with that induced in the resistant G-B1 strain. Osteopetrosis, stunting and lymphoid organ atrophy were more severe in BLH than in CB chickens. G-B1 animals remained superficially normal until the end of the experiment. In contrast to the other two strains, the histopathological changes were very mild and there was no sign of immunosuppression. After 4 months, however, nephroblastomas could be detected in more than 50 per cent of the infected G-B1 chickens. Similar tumors were also found in CB birds kept for up to 5 months. Antibodies against MAV-2-O specific viral proteins were detected in plasma from infected G-B1 chickens but the titers were less than in plasma of convalescent birds. Virus could be demonstrated in peripheral blood until the end of the experiment (at 8 weeks). Therefore the resistance of the G-B1 strain is due neither to a restriction at the receptor level nor the result of a humoral immune reaction, but represents a new type of relative resistance at the cellular level. From (CC X G-B1)F1 and (CC X G-B1)F2 crosses the resistant phenotype is determined by a single genetic factor. This gene is not linked to the major histocompatibility complex. There is also a sex-dependent factor, possibly hormonal, involved in the resistant phenotype.

Anemia↗
PubMed1986

Mechanisms of transplantation tolerance in B-cell-chimeric chickens. Impairment of tolerance by T cell growth factor.

Transplantation tolerance was induced in cyclophosphamide-treated, B-cell-depleted chickens by transfer of allogeneic bursal cells. To study the presence of specific suppressor cells in tolerant birds, mitomycin-C-treated peripheral blood lymphocytes (PBL) from tolerant recipients were cocultured in mixed lymphocyte cultures of normal syngeneic responder and allogeneic stimulator cells. No evidence of suppression was detected, since responses in cultures with tolerant cocultured cells were on the same level as the mixed lymphocyte reaction (MLR) of normal responders without cocultured cells. However, responses in cultures with normal cocultured cells were significantly higher. If cocultured cells were not treated with mitomycin C, responses to tolerizing alloantigen were equally high in cultures with tolerant cocultured cells as in cultures with normal cocultured cells. Likewise, when lymphocytes from tolerant chickens were mixed with normal syngeneic cells in graft-versus-host (GVH) splenomegaly assay, no suppression was detected, but the GVH reaction was even stronger than the reaction induced by the mixture of cells from two normal chickens. Furthermore, administration of chicken T cell growth factor (TCGF) into the cultures enhanced considerably the MLR of tolerant cells against the tolerizing alloantigen, but not against syngeneic or third-party stimulator cells. These results indicate that the transplantation tolerance in B-cell-chimeric chickens is due to lack of alloantigen-specific helper cells. When exogenous help is offered to tolerant cells either by normal syngeneic cells or by exogenous TCGF, the reactivity of tolerant cells against the tolerogen is reestablished.

Animals↗
PubMed1986

Chicken T-cell growth factor: use in the generation of a long-term cultured T-cell line and biochemical characterization.

Supernatants from concanavalin A (Con A)-stimulated chicken spleen cells were used to generate a long-term cultured cell line from antigen-primed chicken peripheral blood leukocytes. This line has been kept in continuous proliferation in vitro for more than 25 weeks. Morphologically these cells were lymphoblastoid and expressed class I and class II antigens of the major histocompatibility complex as well as T-cell (but not B-cell or macrophage) antigens. In addition they contained no peroxidase or non-specific esterase activity, neither were they phagocytic. Proliferation of the line was totally dependent on exogenous T-cell growth factor (TCGF) activity provided by the Con-A-stimulated spleen cell supernatant, comparable with the proliferation of Con-A-induced T-cell blasts. TCGF activity from the supernatant was absorbed both by the long-term cultured T cells and by Con A blasts, demonstrating the presence of receptors for the same TCGF species on the two populations. We have used the long-term cultured cell line to characterize chicken TCGF further. The molecular weight of the biologically active fractions found by gel filtration on Sephadex G-100 was approximately 13,000 and isoelectric focusing showed chicken TCGF to have a pI of pH 5.9. We propose that the TCGF described here is the chicken analogue to the mammalian interleukin 2.

Animals↗
PubMed1985

Clones of B lymphocytes in individual follicles of the bursa of Fabricius.

To discover whether individual bursal follicles can contain clones of B lymphocytes, we estimated the numbers of lymphoid cell precursors populating single follicles in two types of chicken chimera. The first type was produced by establishing parabiotic connections between blood vessels of embryo chorioallantoic membranes. Under these conditions, and most likely during normal development, most follicles are populated by more than one, but less than ten, precursor cells. However, in a second type of chimera, a cyclophosphamide-treated chick reconstituted with normal bursal cells, most follicles in the reconstituted bursa are clonal (their lymphocytes are derived from a single precursor cell). Individual follicles can readily be isolated from bursae of reconstituted birds and should be useful in studies of B cell development.

Animals↗
PubMed1985

Immunoglobulin-bearing stem cells for clones of B (bursa-derived) lymphocytes.

Treatment of neonatal chickens with cyclophosphamide depletes bursal lymphocytes while maintaining the bursal epithelium intact. The bursae of normal young chickens contain "bursal stem cells" which can reconstitute the lymphoid compartment in the bursa of the cyclophosphamide-treated recipient. Using bursal stem cells from IgM allotype-heterozygous donors we show that most bursal follicles in the reconstituted host are colonized by single stem cells which are committed to the expression of one or other IgM allotype. In addition we show that the reconstituting bursal stem cells express allelically excluded surface IgM at the time of transfer. Our results suggest that B lymphocyte numbers in hatched chickens are maintained by self-renewal of committed precursors rather than by de novo production from multipotential stem cells.

Animals↗
PubMed1985

Lymphoid cell chimerism and transplantation tolerance induced by bursal and postbursal cells.

Transplantation of allogeneic bursal cells into cyclophosphamide-treated, immunodeficient chickens is a useful experimental model for analyzing the mechanisms of transplantation tolerance, especially because transplanted bursal cells do not produce graft-versus-host disease. In this study we have determined B-lymphoid chimerism in various lymphoid organs after transplantation of allogeneic bursal stem cells or postbursal cells, and used a variety of tests to determine presence of immunological tolerance. Transplanted bursal stem cells induced a state of stable chimerism that could easily be detected in peripheral blood and other lymphoid organs. Chimerism induced by postbursal cells was low in peripheral blood, but clearly observable in other lymphoid organs, especially in spleen and thymus. Both bursal and postbursal cells induced specific unresponsiveness to donor-line alloantigens. Bursal cell recipients accepted donor line skin grafts--and their graft-versus-host reactivity, as assayed by embryonal splenomegaly, and mixed lymphocyte reactivity against donor line alloantigens were significantly decreased. Despite differences in chimerism, a strong transplantation tolerance was readily induced with bursal stem cells and with postbursal cells.

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