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Biomedical subjects

C S David

Publications and source records attributed to C S David.

At least 217 records · Page 12Linked to original sources
PubMed1985

An idiotope expressed on a monoclonal antibody specific for human haemoglobin beta chain and naturally occurring immunoglobulin(s).

HId-1A (gamma 1:kappa), HId-2a (mu:kappa) and HId-4a (gamma 1:kappa) monoclonal anti-idiotopes of BALB/c origin were induced by the human haemoglobin-reactive, B10.D2-derived monoclonal antibody Hb-2d. HId-1a and HId-4a seem to react with the same idiotope and may, in fact, be encoded by the same V, D and J genes. HId-2a, on the other hand, seems to react with an idiotope different from that recognized by the other two anti-Id's and present in the sera of non-immune B10-H-2 congenic mice. HId-2a, but not HId-1a or HId-4a, may react with an idiotope in or near the antigen binding site of Hb-2d. Naturally occurring immunoglobulin carrying the HId-2a idiotope was affinity-purified from the pooled sera of B10-H-2 congenic mice and partially characterized. It possesses primarily the gamma 2b heavy chain, but small amounts of gamma 1, gamma 2a and mu heavy chains are also detectable. The kappa and lambda 1 light chains are both present in significant amounts. In addition, the affinity-purified immunoglobulin is unreactive with human haemoglobin, is not a rheumatoid factor and does not express in detectable amounts the idiotope recognized by HId-1a and HId-4a. It is possible that all or some part of this polyclonal reagent is specific for antigens normally present in the environment.

Animals↗
PubMed1985

Type II collagen-induced arthritis in mice. III. Suppression of arthritis by using monoclonal and polyclonal anti-Ia antisera.

Pretreatment of mice genetically susceptible to type II collagen-induced arthritis (CIA) with monoclonal or polyclonal antisera specific for I region gene products (Ia antigens) suppressed or delayed the onset of CIA, whereas pretreatment with anti-Ia to an irrelevant haplotype was without effect. The humoral response to type II collagen was transiently depressed 14 days after immunization but antibody levels did not differ significantly after 28 days. The peak delayed-type hypersensitivity to type II collagen was unaffected by anti-Ia treatment. Monoclonal antibody of one anti-Ia specificity enhanced both the antibody response and the arthritis incidence in one mouse strain.

Animals↗
PubMed1985

AKR/J gene(s) unlinked to H-2 determines dominant inheritance of lymphocyte hyporesponsiveness to acetylcholine receptor.

Mice with the H-2b major histocompatibility complex haplotype are high immune responders to nicotinic acetylcholine receptors (AChR), whereas mice with the H-2k haplotype are generally low responders. F1 progeny of C57BL/6 (H-2b) mice crossed with mice of most H-2k strains are high responders to AChR in standard conditions of testing helper T cell proliferation in vitro (4 X 10(5) lymph node cells/microwell, 1 wk after primary challenge in vivo). In contrast, the F1 progeny of AKR/J (H-2k) crossed with high responder (H-2b) strains (B6, A.BY, or C3H.SW) were all hyporesponsive to AChR when lymphocytes were tested at 4 X 10(5) cells/well. However, at a density of 1 X 10(6) or greater/well, a high level of antigen-specific responsiveness was demonstrable in the F1 hybrid lymphocytes. A shift from low to high responsiveness to AChR at high cell densities was observed also in the H-2b strain AKR.B6. Other strains previously demonstrated to be low responders to AChR did not become responsive to AChR when lymphocyte numbers were increased to 1.4 X 10(6)/well. The N2 generation yielded by backcrossing (AKR X B6)F1 mice to AKR/J were all low responders, whereas N2 progeny derived by backcrossing F1 to B6 were high or low responders in a ratio of approximately 1:1 (independent of their H-2 phenotype). Results consistent with this observation were obtained in (AKR X B6) F2 mice. These data suggest that at least one AKR/J gene outside of the H-2 complex exerts a hyporesponsive influence on the I-A-dependent helper T cell response to AChR in H-2b mice.

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PubMed1984

Type II collagen-induced arthritis in mice. II. Passive transfer and suppression by intravenous injection of anti-type II collagen antibody or free native type II collagen.

The passive transfer of high levels of anti-type II collagen antibody from mice with type II collagen-induced arthritis may transfer arthritis to syngeneic recipient animals. However, the transfer of either arthritogenic or sub-arthritogenic doses of polyclonal anti-type II collagen antibody, or non-arthritogenic monoclonal anti-type II collagen antibody may protect mice against the subsequent induction of arthritis by type II collagen. A protective effect was also observed in mice given free native type II collagen intravenously before the administration of collagen in an arthritogenic protocol.

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PubMed1984

Passive transfer of arthritis to mice by injection of human anti-type II collagen antibody.

The serum IgG fraction from a patient with seronegative rheumatoid-like arthritis which contained a high anti-type II collagen antibody titer was injected intravenously into mice susceptible to type II collagen-induced arthritis. A mild, transient, inflammatory arthritis was observed in 20 to 25% of the animals, whereas histologic signs of disease were evident in most of the injected mice. Purified human anti-type II collagen immunoglobulin injected into the knee joints of mice was also shown to induce a transient, inflammatory arthritis. Radiolabeled human anti-type II collagen IgG was shown to accumulate in the peripheral joints of mice, and the specificity of the antibody was shown to be similar to the specificity of anticollagen antibody eluted from the joints of mice with collagen-induced arthritis.

Animals↗
PubMed1984

Mep-1 gene controlling a kidney metalloendopeptidase is linked to the major histocompatibility complex in mice.

Meprin, a glycoprotein with potent metalloendopeptidase activity, is an integral component of the brush border membrane of mouse kidney. Previously we reported that genealogically related inbred mouse strains (C3H and CBA) are markedly deficient in the activity of this enzyme. We report here that meprin deficiency is inherited as an autosomal recessive trait and that several other inbred strains also express low levels of meprin activity. All of the inbred strains deficient in meprin activity are of the H-2k haplotype; however, two strains of this haplotype (C58 and C57BR/cd) expressed normal levels of the proteinase. Congeneic and recombinant mouse strains were examined to determine whether the deficiency was linked to the H-2 complex. The gene controlling the activity of meprin (Mep-1) maps on chromosome 17 to the right of the D end of the major histocompatibility complex. The Mep-1 gene is closely linked to a gene that controls isoenzyme patterns of phosphoglycerate kinase (Pgk-2). This work represents the localization of a gene that determines the activity of an integral cellular endopeptidase in mammalian tissues. In addition, the Mep-1 gene is the only identified gene linked to the major histocompatibility complex that regulates a proteinase activity.

Alleles↗
PubMed1984

Genetic control of the immune response to haemoglobin. V. Production and characterization of A beta restricted T cell lines and clones.

Monoclonal anti-Ia inhibition experiments were conducted to confirm and extend genetic mapping data of I-A gene control of immunity to human haemoglobin (Hb). It was found that the A beta gene is of critical importance in conferring immunity to the alpha-chain and beta-chain subunits of Hb. A possible involvement of I-E region genes in B10.D2 mice to beta-chain is discussed. Through the use of an alpha-chain specific T cell clone data, is obtained indicating that an intact Ia.8+ A beta chain is necessary for antigen presentation in vitro.

Animals↗
PubMed1984

Endogenous synthesis of Ia antigens by a cloned T cell line.

The four Ia polypeptides in mice, A alpha, A beta, E beta, and E alpha, are expressed predominantly on B lymphocytes and certain macrophage populations. Whether T lymphocytes express Ia antigens has been controversial. Although Ia antigens have been demonstrated on small populations of mitogen-activated and alloreactive lymphocytes, the T cell origin of these Ia antigens has been doubted. It has been suggested that Ia antigens on T cells are passively acquired from non-T lymphocytes. The present study analyzes the endogenous synthesis and expression of Ia antigens by an alloreactive-derived T cell clone. This clone, PLT-24.2.Cl, was derived initially from an alloreactive cell population, B6 anti-B10.K. The cell line was cloned by limiting dilution and maintained by periodic boosting with the stimulator cells. After 4 months of sequential boosting, it was possible to maintain the cloned cells in the absence of irradiated B10.K filler spleen cells. It has now been in culture for over a year in the absence of both filler cells and exogenous growth factors (e.g., IL-2). The expression of Ia antigens on the cell surface of the cloned T cell line was detected by using monoclonal antibodies and cytofluorometry. The cloned cells were positive for Thy.1, Lyt.1, and Lyt.2, and negative for surface immunoglobulin. The cells expressed all of the Ia antigens normally found on an I-Ab derived cell, i.e., Ia.8 and Ia.15, and lacked Ia.7. The cells lacked any of the Ia antigens expressed on the original stimulator cells, B10.K. These results show that PLT-24.2.Cl expresses syngeneic Ia antigens. The endogenous synthesis of Ia antigens by these cell lines was confirmed by biosynthetic labeling with radiolabeled amino acid precursors and indirect immunoprecipitation on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. The Ia antigens synthesized by the T cell clone are structurally identical to those synthesized by the syngeneic B lymphocytes, as shown by tryptic peptide mapping using high-pressure liquid chromatography. These studies prove that the Ia antigens predominantly expressed on B lymphocytes and some macrophage-derived cells can also be synthesized and expressed by T lymphocytes. Since Ia antigens are involved in numerous immune phenomena and cell-cell interactions, this information would have to be taken into account in proposing mechanisms by which Ia-restricted helper and suppressor cells are generated.

Animals↗
PubMed1984

Genetic control of immunity to Trichinella spiralis infections of mice. Hypothesis to explain the role of H-2 genes in primary and challenge infections.

H-2 congenic strains of mice were compared for their ability to expel T. spiralis infections from the small intestine and for their ability to limit the reproduction of adult female worms. B10.M mice (H-2f) expelled both primary and challenge infections more quickly than did the strains B10.Q(H-2q) and B10.BR(H-2k). During a primary infection, expulsion of worms from B10.M mice began before Day 9 post-infection and worm counts differed significantly (P less than .05 Student's t-test) from counts in B10.BR mice on each of Days 12 and 15.B10.Q mice expelled worms more rapidly than B10.BR but worm counts did not differ significantly until Day 15. Whereas B10.M mice responded most quickly to expel worms from the gut, B10.Q mice were most effective in limiting worm reproduction. Female worms harvested from B10.Q mice and cultured for 24 hr in vitro produced significantly fewer newborn larvae than did worms from B10.M or B10.BR mice. Worms from B10.M mice were less fecund than worms from B10.BR, but this difference was not apparent before Day 9 post-infection, and worms from B10.M were always more fecund than worms from B10.Q. Challenge infections 21 days following a priming dose of 200 T. spiralis muscle larvae were rejected very quickly. B10.M mice expelled 65% of their worms during the first 24 h. By Day 6 after challenge, B10.M mice had expelled 84% of their worms; B10.Q and B10.BR expelled 75% and 37% respectively. These results suggest that a rapid expulsion response may be expressed in many different strains of mice depending on how the mice are immunized and the size of the infecting dose. Fecundity of female worms 6 days following a challenge infection was reduced for all strains tested when compared to primary infection controls; however, worms from B10.Q mice were less fecund than worms from B10.M or B10.BR. Results of these experiments demonstrate that H-2 genes play an important role in controlling the immune response which expels worms from the gut and the response which limits worm reproduction. These H-2-controlled differences are expressed during both primary and challenge infections. As the present results conflict somewhat with results published elsewhere, we have proposed a new hypothesis to explain the data collected in our laboratories thus far. According to this hypothesis, the anti-adult response, the anti-fecundity response, and the rapid expulsion response are under independent genetic control and influenced by the interacting products of both H-2 and non-H-2 genes.

Animals↗
PubMed1984

H-2-controlled, dose-dependent suppression of the response that expels adult Trichinella spiralis from the small intestine of mice.

H-2 congenic strains of mice expressing the H-2k, H-2q or H-2f haplotype were tested for their ability to expel Trichinella spiralis from the gut following infection with either 100, 150, 200, 400, 500, or 600 L1 infective larvae. H-2q and H-2f mice expelled worms more quickly than H-2k mice when 100-200 L1 larvae were given, but this H-2-controlled effect was much reduced when mice received 400 L1 larvae, and completely eliminated when 500 or 600 L1 larvae were given. The observed dose-dependent delay in the expulsion response was paralleled by a concurrent suppression of lymphocyte responsiveness. Lymphocytes from H-2q mice infected with 100-200 L1 larvae incorporated more [3H]thymidine than did cells from H-2k mice. However, this H-2-controlled difference was not apparent in cells from mice receiving 400-600 L1 larvae. The strongest proliferation response in each case was associated with mice infected with the smallest number of worms. Since strains of mice expressing H-2q or H-2f alleles were suppressed at high doses to a much greater extent than were mice expressing H-2k, H-2 genes must influence this dose-dependent response. Many earlier studies, which failed to demonstrate marked H-2 effects on immunity to T. spiralis, employed infective doses which are shown here to be preferentially suppressive to otherwise resistant strains of mice.

Animals↗
PubMed1983

Regulation of granulomatous inflammation in murine schistosomiasis. II. T suppressor cell-derived, I-C subregion-encoded soluble suppressor factor mediates regulation of lymphokine production.

In the present study, we extended the analysis of the regulation of inflammatory lymphokine production in mice with schistosomiasis mansoni. Splenic lymphocytes of chronically infected mice were briefly pulsed in vitro by soluble egg antigens, washed, and then cultured overnight. The supernatant culture fluid added to cultures of splenic cells of acutely infected or peritoneal lymphocytes of antigen-sensitized mice inhibited the production of migration inhibition factor (MIF). Elaboration of MIF suppressor factor (MIF-SF) required the Lyt-1-,2+,3+ subset of T lymphocytes. MIF-SF acted only on egg antigen-primed cells and required H-2 compatibility with the target cell for its suppressive effect. Further analysis with recombinant strains revealed that the factor interacted with I-AB or I-C subregion-compatible target cells. Experiments using immunoadsorbent columns with bound anti-I subregion alloantisera indicated that MIF-SF contained I-C subregion-encoded determinants. Extrapolation of this in vitro model to in vivo conditions would indicate that the granulomatous response is modulated by I region-derived suppressor factor(s) that regulate lymphokine production by TDH effector cells.

Animals↗
PubMed1983

Cloned T cells recognize Trichinella spiralis antigen in association with an Ek beta Ek alpha restriction element.

A method is described for the production of T-cell lines and clones specific for solubilized Trichinella spiralis antigens. These T cells are antigen-specific and do not respond to challenge with a third party antigen (lysozyme). The proliferation responses of the cloned T cells are specifically inhibited by anti-I-E but not by anti-I-A subregion monoclonal reagents. The inhibition patterns obtained are consistent with cis-gene complementation in B10.K cells involving the Ek beta-chain and the Ek alpha-chain of the I-E molecule. Inhibition is obtained with an Ek beta-specific monoclonal antibody (H9-14.8) but not with an Ak beta-specific monoclonal antibody (10-2.16). Inhibition was also observed with Ia.7-specific (H40-242) or Ia.22-specific (17-3-3) monoclonal antibodies. The inhibition patterns were confirmed by antigen presentation experiments using recombinant inbred mice. Only B10.K (Ek beta Ek alpha) spleen cells and not B10.A(5R) (Eb beta Ek alpha) or B10.S(9R) (Es beta Ek alpha) spleen cells could effectively present T. spiralis antigens. The role of "hybrid" Ia molecules in the immune response to T. spiralis is discussed.

Alleles↗
PubMed1983

H-2 haplotypes, genes and antigens: second listing. II. The H-2 complex.

In this second part of the Second Listing, we describe genes that constitute the H-2 complex proper. Here, we define the complex functionally as consisting of class I and class II loci (see Klein et al. 1983a). The H-2-associated complement loci and the Neu-1 locus have been described in the first part of the Second Listing (Klein et al. 1982), but for completeness we list them here again in some of the tables. We include into the H-2 complex the cluster of Qa and Tla loci, which we consider as class I loci (Klein et al. 1983). The genetic map of the definitely established loci appears in Figure 1 and is based on the recent results of molecular genetics studies (Steinmetz et al. 1982 a, b). For historical reasons we also describe loci (regions, subregions) that were once thought to be part of the H-2 complex but either they have since been withdrawn, or their actual existence is at present uncertain. We first list loci (regions, subregions) that have been designated by capital letters (we call it Madman's Alphabet because of the frivolity with which symbols have been introduced and then withdrawn again), and then other loci believed to be associated with the H-2 complex. As in the First Listing (Klein et al. 1978), the core of the review in the Second Listing constitutes the tables of H-2 haplotypes, antigens, and determinants.

Animals↗
PubMed1983

MHC epitopes of KS and Dd restrict the same population of cytolytic T lymphocytes.

When A. SW (H-2S) mice are immunized with B10.S (H-2S) epidermal cells, cytolytic T lymphocytes are evoked that efficiently lyse B10.D2 (H-2d) as well as B10.S target cells. Immunogenetic analysis of this apparent H-2-unrestricted killing revealed that the most plausible explanation was a sharing of an H-2-restricting epitope by H-2KS and H-2Dd molecules.

Animals↗
PubMed1983

Trichinella spiralis: role of non-H-2 genes in resistance to primary infection in mice.

Two strains of mice which share identical H-2 genes but differ in their genetic backgrounds were compared for their ability to resist infection with Trichinella spiralis. The two strains of mice, C3HeB/FeJ and AKR/J, share the H-2k haplotype which is associated with susceptibility to primary infection with T. spiralis in H-2 congenic strains of mice. AKR/J mice, infected with 150 infective muscle larvae, harbored significantly fewer muscle larvae 30 days postinfection than did mice of the strain C3HeB/FeJ. Approximately equal numbers of worms establish in the small intestine of AKR and C3H mice, but the AKR mice expelled adult worms from the gut more rapidly than did mice of the C3H strain. By Day 9 postinfection, 50% of the worms had been expelled by the AKR mice whereas expulsion of worms from C3H mice was delayed beyond Day 9 and occurred primarily between Days 10 and 12. Over this same experimental period (Days 6-12), fecundity of female worms from AKR mice, measured as the mean newborn larvae/female/hour, was approximately one-half that of worms taken from C3H mice. These results support the conclusion that genes outside of the mouse H-2 complex regulate expulsion of adult worms from the gut. These background genes also markedly influence the fecundity of female worms.

Animals↗
PubMed1983

Cross-reactions of anti-I-Ek monoclonal antibodies with subsets of I-Ab molecules.

Monoclonal antibodies H9-15.4 and H39-459 were derived from an A.TH anti-A.TL immunization. Antibodies H9-15.4 and H39-459 were found to be directed against the I-Ek molecule with positive reactions against B10.A (AkEk) and B10.S(9R) (AsEk) but not B10.A(4R) (AkEb). The monoclonal antibodies were also found to react with the b and q haplotypes, which do not express an I-E molecule. Sequential precipitation analysis showed that in the b haplotype, H9-15.4 and H39-459 react with the I-Ab molecule. These results showed that H9-15.4 and H39-459 recognize determinants shared by I-Ek and I-Ab molecules, suggesting that I-A and I-E molecules may have a common evolutionary origin, possibly through gene duplication. Sequential immunoprecipitation analysis of I-Ab molecules precipitated by H9-15.4 and H39-459 also suggested that these monoclonal antibodies recognize subsets of I-Ab molecules. Pretreatment with the 17-227 monoclonal anti-I-Ab antibody (Ia.15) had no effect on I-Ab molecules precipitated by H9-15.4 and H39-459. Also, pretreatment with H9-15.4 and H39-459 had no effect on I-Ab molecules immunoprecipitated by 17-227. Also H9-15.4 and H39-459 only partially cleared Ia molecules immunoprecipitated by each other. These results suggest that 17-227, H9-15.4, and H39-459 detect a minimum of four subsets of I-Ab molecules. To account for these observations, it is proposed that during evolution of the mouse H-2 complex, in addition to gene duplication of ancestral gene(s) to yield the genes encoding E alpha A alpha, A beta, and E beta polypeptide chains, further gene duplication occurred, forming multiple copies of genes encoding each Ia polypeptide chain.

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