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Biomedical subjects

L Geng

Publications and source records attributed to L Geng.

84 records · Page 5Linked to original sources

A study on proliferative responses to host Ia antigens in allogeneic bone marrow chimera in mice: sequential analysis of the reactivity and characterization of the cells involved in the responses.

Irradiation bone marrow chimeras were established by reconstitution of lethally irradiated AKR mice with C57BL/10 marrow cells to permit serial analysis of the developing reactivities of lymphocytes from such chimeras, [B10----AKR], against donor, host, or third party antigens. We found that substantial proliferative responses to Ia antigens of the recipient strain and also to third party antigens were generated by the thymocytes obtained from the irradiation chimeras at an early stage after bone marrow reconstitution. The majority of the responding thymocytes had surfaces lacking demonstrable peanut agglutinin receptors and were donor type Thy-1+, Ly-2-, and L3T4+ in both anti-recipient and anti-third party MLR. In anti-host responses, however, Ly-2+ thymocytes seemed to be at least partially involved. This capacity of thymus cells to mount a response to antigens of the recipient strain declined shortly thereafter, whereas the capacity to mount MLR against third party antigens persisted. The spleen cells of [B10----AKR] chimeras at the same time developed a more durable capability to exhibit anti-host reactivities and a permanent capability of reacting to third party allo-antigens. The stimulator antigens were Ia molecules on the stimulator cells in both anti-recipient and anti-third party MLR. The responding splenocytes were of donor origin and most of them had Thy-1+, Ly-1+2-, and L3T4+ phenotype.

Animals↗

An epitope on class II antigens that is maintained across species barriers and important in immunologic functions.

Serological, functional, and chemical analyses of murine class II antigens were performed using a unique monoclonal antibody, 1E4, which was obtained from a rat-mouse hybridoma. 1E4, which is specific for a monomorphic determinant on HLA-DR antigens in humans and a polymorphic determinant on RT1-Da antigens in rats, detected class II antigens on the cells from mice carrying H-2 haplotypes of b, d, p, q, u, v, k, j, r, but not those with f or s haplotypes. Analysis of two-dimensional gel electrophoresis revealed that 1E4 monoclonal antibody recognized at least Ek/b, d, k and Ab, d molecules. 1E4 blocked the T cell proliferative responses to beef insulin and TGAL in B10 and BALB/c mice, as well as proliferative responses to GLT in BALB/c mice and to PPD in C3H/He mice, as had been demonstrated in other species. Furthermore 1E4 inhibited MLR to stimulator cells that expressed Ab, d or Ek/b, k, d molecules. Taken together, these findings indicate that an epitope detected by 1E4 on class II antigens has been well preserved across species barriers. This epitope may play a major role or be closely related to the functional site that is involved in recognition of nominal antigens by T cells.

Animals↗

Generation of cytotoxic T lymphocyte responses to allo-H-2 antigens in allogeneic bone marrow chimeras histocompatible at the H-2 subregions.

The present study was performed to determine whether H-2 matching is required for full cytotoxic T lymphocyte (CTL) responses to allo-H-2 antigens in allogeneic bone marrow chimeric mice. A number of irradiated, bone marrow-reconstituted chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant strains and AKR recipient mice were prepared. Spleen cells obtained from such chimeras and normal control mice were activated in vitro by culturing them with irradiated stimulator cells. It was shown that spleen cells from [4R----AKR], [(4R X 3R)F1----AKR] or [AQR----AKR] chimeras, which were histocompatible on the left hand-side of the H-21 subregion between donor and recipient mice, generated greater CTL activities than those that were seen with spleen cells of [3R----AKR] or [5R----AKR] chimeras, which were histoincompatible in this region. We were unable to demonstrate suppressor cell activity of the spleen cells of [3R----AKR] chimeras cultured with stimulator cells. Although spleen cells from [3R----AKR] chimeras showed substantial proliferative responses to stimulator cells (MLR) and to Con A and LPS, IL2 activities of supernatants from Con A-activated spleen cells (Con A SN) of the chimeras were significantly lower than those of [4R----AKR] or [(4R X 3R)F1----AKR] chimeras. Furthermore, vigorous CTL activities were obtained with either spleen cells or thymocytes from [3R----AKR] chimeras when rat Con A SN was added to the MLR cultures. These observations suggest that the numbers of precursor CTLs in the cells from [3R----AKR] chimeras are at the same level as those of [(4R X 3R)F1----AKR] or normal mice and that the low CTL activities generated by spleen cells of [3R----AKR] chimeras compared to H-2I-matched chimeras are due in large measure to deficiency in IL2 production by the splenic T cells of the [3R----AKR] chimeras.

Animals↗

A study on location of synthetic site which mainly synthesizes and delivers fifth component of complement system in vivo.

Tissue sites for synthesis of the fifth component of complement (C5) in vivo have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. Our prior studies have demonstrated that bone marrow chimeras which had been prepared by transplanting marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients lacked detectable levels of C5 in the sera. However, when such potentially C5-deficient [C5(+)---C5(-)] chimeras were introduced into their spleens by means of injections of fully dispersed single cell suspensions of hepatocytes isolated from the C5-sufficient donor strain, they accepted the transplantation of hepatocytes for prolonged periods and developed a measurable amount of C5 in the sera. These results indicate that C5 protein in sera is not synthesized in significant amount by cells that are descendants of bone marrow cells but rather that this complement component is synthesized and delivered to the blood in vivo by somatic cells including liver cells that are not derivatives of the bone marrow.

Animals↗

Analysis of synthetic sites of fourth and fifth components of serum complement system in allogeneic bone marrow chimaeras.

Synthetic tissue sites for the fourth and fifth components of complement (C4 and C5) have been investigated using allogeneic bone marrow chimaeras in mice. One group of chimaeric mice was prepared by transplanting bone marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice that produce high levels of C4 into irradiated recipients that are characterized by having low levels of C4 or vice versa. In such chimaeras, lymphoid cells and serum immunoglobulin allotypes were shown to be exclusively of donor origin. However, haemolytic activities of sera from the chimaeras were consistently identical with those of normal mice of the recipient strain. Similar results were obtained when the complement component levels of the sera were evaluated by double diffusion assays. C4 or C5 antigens were detected in sera of the chimaeras only when recipients were strains that are characterized by having high C4 level or were C5-sufficient mice, respectively. These findings indicate that circulating C4 or C5 complement components present in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimaeric mice.

Animals↗

[A study on the location of synthetic sites of the fourth and fifth components of the complement system in allogeneic bone marrow chimeras and hepatocyte transplantation chimeras].

In this study, the tissue sites for synthesis of fourth and fifth components of complement (C4, C5) have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. One group of chimeric mice was prepared by transplanting bone marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice which produced high level of C4 into irradiated recipients which were characterized by having low level of C4 or vice versa. The results showed that C4 or C5 antigens were present in the sera of the chimeras only when recipients were strains which were characterized by having high C4 level or were C5-sufficient mice, respectively. These findings indicate that circulating C4 and C5 in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimeric mice. However, when hepatocytes isolated from the C5-sufficient strain were inoculated into the spleens of C5-deficient bone marrow chimeras, detectable amounts of C5 were present in the sera. These results indicate that C5 protein is synthesized and delivered to the blood in vivo by liver cells.

Animals↗

Analyses of Ia restriction specificity of helper T cells in H-2 subregion compatible bone marrow chimera in mice.

Using irradiation bone marrow chimeras which had partial compatibility in H-2 subregions between donor and recipient mice, we found that H-2I matching was sufficient for the chimeras to generate anti-sheep erythrocyte plaque-forming cell (PFC) responses. In such chimeras, T cells appeared to encounter appropriate partner cells bearing the same Ia antigens as those which they had learned to recognize as self in the recipient micro-environment. Furthermore, the PFC number seen in I-A compatible chimeras was only about half of that seen in I-A, I-E compatible chimeras, suggesting the existence of two independent subpopulations of helper T cells. When incompatibility of donor and recipient mice existed on the left side of the H-2I region, the responses were very weak. However, even in such chimeras, marked responses were observed for both IgM and IgG type PFC following a sufficient period after immunization. This observation appears to indicate the existence of a minor subpopulation of helper T cells which can expand and interact effectively with antigen presenting cells of donor type.

Animals↗

H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s).

To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented.

Alleles↗

Analysis of contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) in allogeneic bone marrow chimaera in mice.

Irradiated C57BL/6 (B6) and C3H mice were reconstituted with bone marrow cells from BALB/c mice. The chimaeric mice, [BALB/c----B6] and [BALB/c----C3H], developed and expressed contact sensitivity to DNFB. The in vivo responses paralleled to proliferative responses of regional lymph node cells of the chimaeras to DNBS in vitro. Furthermore, intravenous administration of DNBS rendered the chimaeras tolerant to subsequent sensitization with DNFB. The tolerance was transferred to lightly irradiated BALB/c mice by the spleen and lymph node T cells. These results represent marked contrast to our previous observations that [B6----C3H] and [B6----AKR] chimaeras were unable to develop specific unresponsiveness to stimulation with DNFB by the intravenous route. The controversial observations seen in the chimaeras prepared by BALB/c bone marrows and those prepared by B6 cells are discussed.

Animals↗

Clinical observations on Behçet's disease in Tianjin, China.

Frequency and clinical manifestations of Behcet's disease were investigated in the Teaching Hospital of Tianjin Medical College, China. Diagnosis of Behcet's disease was made according to the diagnostic criteria proposed by the Japanese Research Committee on Behcet's disease. Forty-two patients, 14 men and 28 women, were found to have Behcet's disease. Fourteen patients belonged to the complete type and 28 to the incomplete type. Frequency of ocular lesions, especially in women patients, was lower and that of genital ulcers higher in China than those in Japan. Epidemiological and anthropological significance for the development of this disease was discussed.

Adolescent↗