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Y M Kong

Publications and source records attributed to Y M Kong.

At least 37 records · Page 2Linked to original sources
PubMed1985

Characterization of the in vitro murine T-cell proliferative responses to murine and human thyroglobulins in thyroiditis-susceptible and -resistant mice.

The in vitro proliferative response to autoantigenic mouse thyroglobulin (MTg) of lymph node cells (LNC) from thyroiditis-susceptible (high-responder) CBA/J (H-2k) mice was further characterized. The relatively weak response was enhanced by adding irradiated spleen cells from normal syngeneic mice to cultures of responding LNC. Furthermore, the adjuvant used for immunization was found to influence the magnitude of the response. Results of experiments varying both the adjuvant and the route of immunization (footpad versus subcutaneous) demonstrated that marked proliferative response to MTg in vitro was not necessarily a predictor of the severity of disease. However, the capacity to proliferate in response to MTg correlated with disease susceptibility, as reported previously. The response to MTg was dependent on Thy-1+, Lyt-1+2- cells and was inhibited by monoclonal I-A antibodies. Thus, proliferation is mediated by T cells of the helper/amplifier phenotype recognizing the autoantigen in association with Ia molecules. The determinants on human thyroglobulin (HTg) and MTg stimulating the proliferative responses of LNC from thyroiditis-susceptible and thyroiditis-resistant (low-responder) BALB/c (H-2d) mice were found to differ. Cells from resistant mice proliferated only in response to foreign determinants on HTg and not to shared or mouse-specific epitopes of MTg, whereas susceptible mice had T cells reactive to shared determinants expressed on MTg and HTg as well as to foreign determinants on HTg.

Adjuvants, Immunologic↗
PubMed1984

T-cell subsets in the thyroids of mice developing autoimmune thyroiditis.

To examine the role of T-cell subsets in the development of thyroid lesions, female CBA/J mice were immunized with 60 micrograms mouse thyroglobulin (MTg) in 0.1 ml complete Freund's adjuvant in both hind footpads. The thyroids were removed 12-21 days later, pooled, and dispersed. The cell suspension was examined by membrane immunofluorescence for the distribution of Thy-1+, Lyt-1+, Lyt-2+, and sIg+ lymphocytes. For comparison, peripheral blood leukocytes (PBL) from the same animals were similarly examined. Throughout this 10-day interval, B cells in the thyroid were consistently below 5%, whereas B cells represented 19-24% of PBL. Thy-1+ cells in PBL ranged from 45 to 59%, whereas Thy-1+ cells in the thyroid were 37-50%. However, only thyroidal T cells showed a consistent decline with time and were replaced gradually by cells without T or B cell markers. In particular, there was a clear shift in the Lyt-1+:Lyt-2+ ratio from about 7 down to 2 in the thyroid as the early predominance of Lyt-1+ cells was followed by a relative increase in Lyt-2+ cells. Our results show that there is an accumulation of Lyt-1+ and Lyt-2+ cells in the infiltrated thyroid. These cells may include MTg-reactive, helper, and cytotoxic T cells which localize (or differentiate) in the thyroid and initiate the lesions.

Animals↗
PubMed1984

Injection of mouse thyroglobulin and/or adult thymectomy do not break tolerance to thyroglobulin during the lupus like graft versus host disease in mice.

In a previous paper (Gleichmann, van Elven & van der Veen, 1982), it had been reported that, in contrast to lupus like autoantibodies such as anti-DNA, autoantibodies to mouse thyroglobulin (MTg) were not detectable in serum of F1 mice suffering from a lupus like graft versus host disease (GVHD) (GVH F1). In the present paper, possible explanations for this restricted autoantibody formation during the potent allogeneic stimulation were investigated. The main question was whether the natural level of circulating MTg was too low to induce the formation of anti-MTg antibodies in GVH F1 mice. Existence, in the F1 mice studied, of B cells capable of producing anti-MTg antibodies was demonstrated by injection of lipopolysaccharide (LPS) and exogeneous MTg. However, MTg injected into various F1 mice at the onset of the GVH reaction (GVHR) failed to overcome the lack of antibody formation to MTg even though the GVHR led to a severe lupus like disease. Furthermore, adult thymectomy (ATx) of either the recipients, the donors, or both also did not break tolerance to MTg during the GVHR, irrespective of administration of exogeneous MTg. Thus, neither intravenous injection of MTg nor ATx, designed to remove T suppressor (TS) cells, is adequate to enable an autoantibody response to MTg during lupus like GVHD. Hence, the non-specific T cell help that causes lupus like GVHD seems to be intrinsically insufficient to trigger the Tg reactive B cells. We suggest that globular proteins, such as Tg, require specific T cell help. In the presence of only non-specific T help, self-antigens such as DNA seem to be more apt than globular proteins to provide an effective signal 1 to the corresponding autoreactive B cells.

Animals↗
PubMed1983

Experimental autoimmune thyroiditis. In vitro cytotoxic effects of T lymphocytes on thyroid monolayers.

Effector mechanisms in experimental autoimmune thyroiditis (EAT) were studied in vitro by establishing a cytotoxicity system with thyroid target cells. Lymph node cells (LNC) from popliteal and inguinal lymph nodes were obtained from CBA/J mice (8-10 wk old) 12-18 d after immunization with 120 micrograms mouse thyroglobulin (MTg) in complete Freund's adjuvant (0.2 ml to both hind footpads and thighs) and were cultured with MTg (10-50 micrograms/ml). On day 5 of culture, viable LNC were added to labeled thyroid monolayers and their cytoxicity was assayed after 16 h. Functional thyroid target cells, as reflected by MTg production for up to 9 d, were prepared by adding 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate and 60 microU thyroid-stimulating hormone/ml to the culture medium. On days 5-7, confluent monolayers were labeled with 111In and used as targets. Specific 111In-release ranged from 56 to 85%. The cytotoxic response is MTg specific and H-2 restricted. Pretreatment of thyroid target cells with rabbit antiserum to MTg completely inhibited cytotoxicity. Pretreatment with mouse antiserum to either Kk or Dk products resulted in approximately 50% inhibition, whereas the combined use of both antisera led to total inhibition. No cytotoxicity was observed when control BALB/c thyroid cultures were the target cells. The kinetics of the expansion of Thy-1+ cytotoxic cells by in vitro exposure to MTg were then studied. The cytotoxic response required 5 d to develop and was abolished by treating LNC on day 4 with monoclonal antibody to Lyt-1.1, but not to Lyt-2.1, plus complement. In contrast, by day 5, cytotoxicity was abrogated by similar treatment with antiserum to Lyt-2.1, but not to Lyt-1.1. We conclude that cytotoxic cells derived from MTg-immunized mice are Lyt-2-bearing cells but require the presence of Lyt-1-bearing cells for their generation and/or differentiation.

Animals↗
PubMed1983

Suppressive effects of soluble histocompatibility antigens on the in vitro generation of cytotoxic T cells to D-end alloantigens.

Murine histocompatibility antigens were solubilized from the spleens and lungs of C57BL/6 (H-2b) animals with hypertonic salt (3 M KC1). Aggregate-free soluble antigens were incubated with nonadherent lymph node cells from BALB/c (H-2d) mice for 18 hr prior to their use as responder cells in the mixed-lymphocyte reaction (MLR). It was found that the generation of cytotoxic cells was suppressed while the proliferative response was not affected. The observed suppression was not due to a shift in the kinetics of the generation of cytotoxicity as determined throughout a 10-day culture period. The suppression was specific in that the response in MLR to unrelated H-2f stimulator cells and the subsequent generation of cytotoxic cells were unchanged. Using various H-2 recombinant strains as target cells in the assay of cell-mediated lympholysis, suppression of cytotoxicity was observed when the D end, but not the K end, was shared with the C57BL/6 strain from which the antigens were derived.

Animals↗
PubMed1982

Regulation of experimental autoimmune thyroiditis: influence of non-H-2 genes.

Experiments were conducted to investigate the non-H-2 genetic effects on experimental autoimmune thyroiditis (EAT). Strains having C3H or BALB background in general produced higher autoimmune responses to mouse thyroglobulin (MTg) than the B10 or A strains. Comparisons of C3H and B10 congenic strains carrying similar H-2 haplotypes demonstrated that the C3H congenics had significantly higher MTg antibody titres and more severe thyroid damage, even when the strains carry the low responder H-2 haplotypes. These observations show that non-H-2 gene(s) influences EAT, in addition to genes in the MHC.

Animals↗
PubMed1981

Syngeneic thyroglobulin is immunogenic in good responder mice.

Mouse thyroglobulin (MTg) or thyroid extract (TE) was given repeatedly to good responder C3H/Anf (H-2k) and poor responder BALB/c (H-2d) mice in the absence of adjuvant. Anti-MTg antibodies reached high levels in good responder mice given high doses of thyroid antigen. To eliminate stimulation by alloantigenic determinants and reduce the chance of denaturation. TE from syngeneic mice was prepared freshly each week and injected into good and poor responder strains. Again, significant antibody titers were observed in good responder mice. The antibody was specific for MTg since (a) it was not inhibited by extracts of other organs and (b) it reacted strongly with the closely related rat Tg and weakly with Tg from other species. Histology revealed mononuclear cell infiltration of the thyroid of good responder, but not of poor responder mice, regardless of the strain used to provide the thyroid antigen. The data demonstrate the presence of both T and B cell populations reactive with this self antigen and their stimulation by repeated high doses of antigen, without the aid of adjuvant, to override the regulatory controls that normally prevent autoimmune responses.

Animals↗
PubMed1977

Studies on interference with tolerance induction in T cells.

The mechanism of T-cell tolerance to a thymus-dependent antigen was examined, using the adjuvant polyadenylic-polyuridylic acid (poly A:U). In adoptive transfer experiments, thymus cells obtained from donor mice 2 days after treatment with a tolerogenic dose of bovine gamma-globulin (sBGG) did not cooperate with bone marrow (BM) cells in irradiated recipients challenged with aggregated BGG (aBGG). In contrast, thymus cells from donors given sBGG plus poly A:U retained their helper activity, as assayed by hemagglutination and rosette formation of spleen cells. The effect of poly A:U in preventing tolerance induction was also demonstrable in the cortisone-resistant population, in that thymus cells from cortisone-treated donors that had received sBGG and poly A:U retained their helper function. The presence of suppressor cells and the effect of poly A:U on their stimulation were also examined. sBGG-treated thymus cells suppressed the response of BGG-primed spleen cells in lethally irradiated mice, whereas thymus cells from donors treated with sBGG and poly A:U were not suppressive. These observations show that poly A:U prevents tolerance induction and the development of suppressor activity in T cells.

Animals↗
PubMed1977

In vitro tolerance induction to a thymus-dependent antigen with BALB/c and C57BL/6 lymph node cells: effect of tolerogen concentration and duration of exposure.

Further studies on tolerance induction in vitro to bovine gamma globulin (BGG) in nonadherent BALB/c lymph node cells showed that it was dependent upon both the dose of tolerogen and the time of exposure. Nearly complete tolerance was achieved at a dose of 1.0 mg/ml and an incubation time of 12-18 hours. When C57BL/6 strain was used for comparison with the BALB/c strain because of its relative ease to become tolerant after in vivo injection of tolerogen, the rate of tolerance induction of its nonadherent lymph node cells was not different from that of BALB/c cells. Thus, in the absence of other host factors, the acquisition of tolerance by lymphocytes is gradual and may reflect the time required for a cell to reach a susceptible phase of the cell cycle and/or the activation of suppressor cells.

Animals↗