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C S David

Publications and source records attributed to C S David.

At least 181 records · Page 10Linked to original sources
PubMed1989

Identification of T-cell receptor V beta deletion mutant mouse strain AU/ssJ (H-2q) which is resistant to collagen-induced arthritis.

Our laboratory is involved in investigating the role of T-cell receptor (Tcr) in collagen-induced arthritis (CIA). During these studies we found AU/ssJ (H-2q) mice to be resistant to CIA like SWR (H-2q), as compared with other H-2q strains with wild-type Tcr like DBA/1 and B10.Q. Upon screening with monoclonal antibodies F23.1 and KJ23a, AU/ssJ was found to be F23.1 negative (V beta 8 Tcr negative) and KJ23a positive (V beta 17a Tcr positive). Southern blot analysis on liver DNA using specific Tcr-V beta probes confirmed the deletion of V beta 8 gene family and also showed that AU/ssJ mice have deletions of V beta 9, V beta 13, V beta 12, and V beta 11 genes of Tcr. Further, these mice show a restriction fragment length polymorphism pattern with V beta 10, V beta 6, and V beta 17 probes similar to SWR mice as compared with B10 mice. Since SWR and AU/ssJ are from different backgrounds, these studies indicate that specific variable region beta chain genes of Tcr are crucial for susceptibility to CIA in mice. Furthermore, these studies identify an additional inbred strain which has also deleted 50% of its Tcr-V beta genes.

Animals↗
PubMed1989

In situ kinetic analysis of thyroid lymphocyte infiltrate in mice developing experimental autoimmune thyroiditis.

L3T4+ T cells from genetically susceptible mice developing experimental autoimmune thyroiditis (EAT) were shown earlier to proliferate in response to restimulation with mouse thyroglobulin (MTg) in vitro and to mediate the adoptive transfer of EAT, whereas Lyt-2+ cells differentiated in vitro into cells cytotoxic for thyroid monolayers. Leukocyte suspensions from disrupted thyroid glands examined on Days 13-21 after immunization revealed the accumulation of both T cell subsets in the infiltrate at varying ratios. To characterize the in situ kinetics of cellular infiltration in chronic EAT, we extended the observation intervals after immunization to include Days 21 to 42. The leukocytes in thyroid sections were labeled immunohistochemically first with rat monoclonal antibodies to L3T4, Lyt-2, Thy-1, k light chain, or F4/80 macrophage antigen, then with biotinylated anti-rat IgG, utilizing the avidin-biotin-peroxidase technique. Throughout the 21- to 42-day interval, no significant variations were detected in the percentages of L3T4+ subset, but those of Lyt-2+ cells increased and then declined. The shift in the L3T4+:Lyt-2+ ratio, down from 2.4 to 1.6 and then up to 3.0, was directly related to changes in the Lyt-2+ subpopulation. The F4/80+ and B cell populations changed little during this period. These findings illustrate the changing kinetics of T cell subsets in situ in the development and perpetuation of EAT and MTg-immunized mice.

Animals↗
PubMed1989

Auto-delayed-type hypersensitivity induced in immunodeficient mice with modified self-antigens. V. Cellular autoreactivity directed against self-H-2Dd subregion mediates the inflammatory responses.

X-irradiated (250 rads) A mice injected with syngeneic trinitrophenylated spleen cells (Syn-TNP-SC) developed syngeneic delayed-type hypersensitivity (Syn-DTH) after footpad challenge with syngeneic concanavalin A-induced lymphoblasts (Syn-Con A blasts), as indicated by footpad swelling and lymph-node proliferation assays. Genetic analysis with different recombinant strains of mouse revealed that the H-2Dd subregion restricts these immunological activities. A small immunogenic entity was isolated from Syn-TNP-SC extract by gel filtration and affinity chromatography with anti-Dd antibody. X-irradiated A mice injected with this antigen also generated inflammatory responses after challenge with Syn-Con A blasts. Analysis of the data obtained from the gel filtration and the affinity chromatography suggest that the Syn-DTH-stimulating antigen is a fragment of the H-2Dd heavy chain with a molecular weight (MW) of 5,000 to 10,000. This fragment does not contain TNP molecules or sugar moieties and neither does it express affinity for antibodies against class II products. Ltk-cells transfected with the H-2Dd gene also induced Syn-DTH in X-irradiated A mice, while the parent cells failed to stimulate such a response. Taken together these findings indicate that the selection process in the thymus is not absolute and T cells recognizing self-major histocompatibility complex (MHC) products do migrate from this organ to the periphery of the immune system. The possible biological significance of these autoreactive cells is discussed.

Animals↗
PubMed1989

Study on the origin of major histocompatibility complex (MHC) genes in recombinant mouse strains by detection of polymorphic variants of MHC class III gene, complement C4.

In recombinant mouse strains the elements of the major histocompatibility complex gene cluster are composed of those of the parental strains. The origin of elements except the S region was previously determined by immunological and biochemical typing methods. For determination of the origin of the S region and the possible location of the recombination event around the S region, Southern blot analysis was performed. By the detection of genetic polymorphic patterns of complement C4 gene in 2 of the 5 recombinant strains the recombination was localized down-stream of the C4 gene and before the D gene region.

Animals↗
PubMed1988

Production of antibodies against murine class II antigens using unconjugated synthetic peptides of the beta chain region 63-78.

synthetic peptides corresponding to residues 63-78 of the first domain of the beta chain of murine I-A/I-E class II antigens were used in the unconjugated rather than the traditional protein-conjugated form to immunize (129J X B6)F1 mice. The sequences made represented the four haplotypes; Ak beta, Ad beta, Abm-12 beta and Ed beta. These sequences were selected on the basis of computer algorithms used to predict surface accessibility and main-chain flexibility profiles, and by reported hypervariability and site-directed mutagenesis experiments of these regions. Factors such as the use of complete Freund's adjuvant, a continuous immunization regime, and the sex of the mice used were found to influence the amount of anti-peptide antibody produced when unconjugated peptide was used as the immunogen. Antibodies produced were shown by FACS analysis to react with I-A/I-E class II antigens expressed on the lymphocyte surface. These findings indicate that the use of unconjugated synthetic peptides representing sequences of proteins which are in close proximity to disulfide bonds may be an advantage over conventional methods of peptide conjugation to proteins.

Amino Acid Sequence↗
PubMed1988

Bone marrow cell transplants involving intra-H-2 recombinant inbred mouse strains. Evidence that hemopoietic histocompatibility-1 (Hh-1) genes are distinct from H-2D or H-2L.

Hemopoietic histocompatibility (Hh) Ag are noncodominantly expressed on bone marrow stem cells and other normal and neoplastic cells of hemopoietic origin. H-2/Hh-1 allogeneic or parental-strain bone marrow grafts are eliminated in a determinant specific manner by NK cells. In inbred mouse strains, seven Hh-1 alleles representing combinations of five different Hh-1 antigenic determinants are described. Each Hh-1 allele maps in the vicinity of H-2D, and the genes that map to Hh-1 are transacting regulatory genes. The expression of a particular determinant depends on the absence of the regulatory gene and the presence of the appropriate structural gene. The primary focus of this study is to ascertain whether the Hh-1 phenotype and the serologic H-2DL typing are always correlated or whether recombinant can separate the two. To achieve this, we used a panel of irradiated hosts that are able to recognize the different Hh-1 determinants on the bone marrow cells of congenic intra-H-2 recombinant donors. We report: 1) the majority of strains show a correlation between Hh-1 and H-2DL: 2) B10.RQDB and B10.WB strains dissociate Hh-1 from Lb: 3) nine H-2S/D interval recombinant strains exhibit no correlation between the H-2DL type and Hh-1 phenotype; and 4) in two strains from this group, B10.D2 (R106) and B10.RSF5, H-2S/D crossovers occurred within Hh-1r, (Hh-1 regulatory). We conclude that Hh-1r is a distinct regulatory locus mapping telomeric of H-2S and centromeric of, although probably closer to, H-2D.

Animals↗
PubMed1988

Immunosuppression of collagen-induced arthritis in mice with an anti-IL-2 receptor antibody.

The use of an anti-IL-2R antibody, 7D4, was investigated in vivo in the suppression of collagen-induced arthritis in mice. 7D4 was shown to reduce the incidence of arthritis in a group of mice immunized with type II collagen as compared with a group similarly immunized with collagen and treated with a control isotype matched anti-Forsmann antibody. 7D4 was also shown to reduce the severity of arthritis in the treated mice as compared to the mice in the group treated with the control antibody. Anti-IL-2R antibodies may be useful in the treatment of autoimmune diseases by selectively suppressing activated T cells.

Animals↗
PubMed1988

Possible role of V beta T cell receptor genes in susceptibility to collagen-induced arthritis in mice.

Arthritis was induced by immunization of type II collagen in adjuvant in mice from H-2q-bearing crosses between SWR (H-2q/q) and B10 (H-2b/b mice), two strains known to be resistant to collagen-induced arthritis (CIA). The resistance of B10 is known to be due to its MHC haplotype, but it was postulated that the resistance of SWR mice which expresses the susceptible MHC haplotype could be due to the deletion of close to 50% of the V beta genes of the T cell receptor (TCR) in them. 17% of the F1 hybrids, 33% of the SWR backcrosses, 68% of the B10 backcrosses, and 52% of the F2 hybrids developed arthritis on follow-up to 5 mo after primary immunization with collagen. There was no significant difference in anti-type II collagen antibody titers between the arthritic and nonarthritic mice in each of these crosses. The segregation of the TCR genes with arthritis was determined in the F2 population by typing with F23.1 mAb that reacts with T cells using V beta 8 subfamily genes in their TCRs. SWR mice are F23.1- as V beta 8 genes are deleted in them. All six of arthritic mice homozygous for H-2q, and thus with an H-2 haplotype similar to SWR mice, expressed the F23.1 marker. These studies indicate that for complete susceptibility to collagen-induced arthritis, not only is a susceptible MHC haplotype (H-2q) important, but possibly also the presence of a subset of T cells using certain specific V beta genes in their TCRs. Other background genes may, however, modulate the severity of arthritis.

Animals↗
PubMed1988

Polymorphism of Hh-1, the mouse hemopoietic histocompatibility locus.

The major goal of these studies is to more fully assess the polymorphism of the hemopoietic histocompatibility (Hh) genetic system. H-2 homozygosity is required for optimal immunogenicity of bone marrow cell (BMC) grafts, and "hybrid resistance" to grafts of parental strain BMC by irradiated H-2 heterozygous F1 hybrid mice suggests that Hh-1 antigens are inherited recessively. The Hh-1 antigens are also expressed on other normal hematopoietic cells and lymphoid tumors, and natural killer cells are the effectors which mediate the elimination of BMC grafts in an Hh-specific manner. Previous studies have demonstrated three different antigens mapping to the Hh-1 locus near H-2D. We test the expression of Hh-1 on BMC of all nonrecombinant H-2 haplotypes of independent origin and H-2j, a presumed natural recombinant. Hh-1 typing is based on the pattern of growth and rejection in a panel of hosts. F1 hybrids with H-2b, H-2d, and H-2k are produced and used as donors and hosts to confirm the phenotype. Grafts of b, d-, and j-haplotype marrow serve as prototypical examples of determinants that are provisionally designated as 1, 2, and 3, respectively. We describe a new determinant, 4, in the k haplotype. It is non-codominantly expressed, maps to H-2D, and is also expressed on H-2b BMC. NZW, H-2z grafts exhibit a phenotype similar to k, but express a unique determinant 5 which can be distinguished from determinant 4. This additional determinant is also expressed by the b haplotype. The d, f, and p haplotypes all express determinant 2, and grafts of j-haplotype marrow are found to express determinants 2 and 5 in addition to determinant 3. The q and r haplotypes are null for all known determinants. Finally, we describe a phenotype which is a new combination of previously described determinants: s-haplotype grafts express determinants 1, 2, and 4. The polymorphism of Hh-1 detected thus far consists of seven alleles which are combinations of five distinct determinants.

Animals↗
PubMed1988

Nematospiroides dubius: two H-2-linked genes influence levels of resistance to infection in mice.

Strains of mice sharing common H-2 haplotypes but different genetic backgrounds, and H-2 congenic strains of mice differing only at H-2 genes were studied to assess the role of H-2 and non-H-2 genes in immunity to challenge infections with the nematode parasite Nematospiroides dubius. Strains of mice sharing the H-2k haplotype were uniformly more susceptible to challenge than strains expressing H-2q alleles, regardless of genetic background. However, in some cases strains of mice sharing the k or q haplotypes differed significantly in levels of resistance. Therefore, non-H-2 genes must influence the response observed. H-2 cogenic strains of mice differed markedly in their ability to resist challenge infections. Mice sharing the C57BL/10 background but expressing k alleles were very susceptible to challenge, while the H-2q, H-2f, and H-2s, haplotypes were associated with resistance. Studies of H-2 congenic recombinant strains of mice suggested that two H-2 genes influence the antiparasite response. One of these genes maps to the left of E alpha and the other to the D-end of the H-2 complex. It is concluded also that the unique configuration of H-2 genes in F1 hybrids contributes to increased resistance to challange.

Alleles↗
PubMed1988

The role of autoreactive T-cell hybridomas from autoimmune model mice.

Autoreactive IL-2-producing T-cell hybridomas were established from New Zealand Black and White (B/W) F1 and MRL/1 mice. In B/WF1 mice the frequency of IL-2-producing hybridomas increased with age. It is necessary for the cells to recognize autologous MHC molecules in order to release IL-2. Inoculation of hybridoma cells into several mouse strains via the footpad produced significant swelling responses in an H-2-restricted manner. Finally, several autoimmune abnormalities were induced in naive H-2-compatible mice by i.v. inoculation of certain hybridoma cells. These results demonstrate that self-MHC molecule recognition by T cells plays an important role in the development of autoimmunity.

Aging↗
PubMed1987

Genetic analysis of the H-2D region using a new intra-D-region recombinant mouse strain.

A rare D-region recombination event which gave rise to the B10.RQDB major histocompatibility complex haplotype has been examined to ascertain the nature of the crossover and to determine which class I genes are present in the new alignment of D-region genes. Serologic analysis have shown that the B10 . RQDB major histocompatibility complex recombinant mouse inherited the H-2Dd gene from the B10.T(6R) parental line and the H-2Db gene from the B10.A(2R) parental line, representing the first example of an intra-D-region crossover resulting from an intercross. Previous molecular genetic analyses of the d and b haplotypes revealed structural diversity in the organization of their D-region gene clusters. Hence, the D region is comprised of five class I genes in the d haplotype and only one in the b haplotype. Because allelic relationships among the various D-region genes are not defined, either a homologous or nonhomologous alignment of genes has generated the RQDB crossover. Therefore, the possibility that all three D-region antigen-presenting molecules (Dd, Ld, and Db) might be encoded by the RQDB haplotype was examined. Fluorescence-activated cell sorter and cytotoxic T lymphocyte analyses revealed no detectable levels of H-2Ld cell-surface expression, confirming earlier studies with antibody-mediated cytotoxicity and immunoprecipitation. Southern blot analysis localized the recombination point to within a 1-kb region at the centromeric end of the H-2Ld gene on the B10 . T(6R) chromosome in a region of high homology to the H-2Db gene on the B10 . A(2R) chromosome. Together, these studies define the D region of the RQDB haplotype as containing the five class I genes: Dd, D2d, D3d, D4d, and Db. In addition to providing insight into rare recombination events in the D region, the B10.RQDB mouse should be a useful tool for exploring the function of D-region genes.

Animals↗