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Biomedical subjects

D G Colley

Publications and source records attributed to D G Colley.

At least 145 records · Page 8Linked to original sources
PubMed1981

Modulation of Schistosoma mansoni egg-induced granuloma formation: I-J restriction of T cell-mediated suppression in a chronic parasitic infection.

Newly formed hepatic granulomas around Schistosoma mansoni eggs become progressively smaller during the chronic (greater than or equal to 15 weeks after infection) phase of the disease. This reduction in granuloma size, termed "modulation," is known to be caused in part by a T lymphocyte that can adoptively transfer modulation to 6-week-infected mice. The present study examines a possible role for the I-J locus in regulating the suppressor T lymphocyte aspects of modulation. Adoptive transfer between congeneic B10.A(3R) and B10.A(5R) mice (differing at the I-J locus) indicated that optimal suppression is dependent upon homology at the I-J locus. In vivo treatment of chronically infected mice with microliter amounts of antiserum specific for the recipient's I-J determinant blocked modulation during chronic infection and prevented adoptive transfer of suppression to 6-week-infected mice. The in vivo regimen of anti-I-J had no effect on anti-schistosomal egg antigen titers during chronic infection. These results demonstrate an I-J restriction for suppression. It appears that the suppressor T lymphocyte circuit responsible for this aspect of modulation requires an I-J positive lymphocyte.

Animals↗
PubMed1981

T lymphocytes that contribute to the immunoregulation of granuloma formation in chronic murine schistosomiasis.

Immunoregulation of Schistosoma mansoni egg-induced granuloma formation in the mouse occurs as chronic infection is being established. Three different modes of manipulation that are known to affect immuno-regulatory T lymphocytes were applied to this model. Adult thymectomy (AdTx) of CBA/J mice, 6 wk after infection, did not affect the size of their granulomas at 8 or 12 wk after infection. However, by 15 wk after infection, sham-treated mice exhibited continued development of modulation of their granulomas, whereas AdTx mice did not. Hemagglutinating antibody titers against soluble egg antigen preparation were marginally elevated in the AdTx group. Adoptive transfer of the suppressor effect of chronic spleen cells was ablated by AdTx. In vivo administration of 1 ml of rabbit anti-mouse thymocyte serum (RAMTS) over a 3-day period to chronically infected mice resulted in a minimal increase in granuloma formation. This treatment was seen, however, to be efficacious in eliminating the suppression normally associated with adoptive transfer of chronic spleen cells. Hydrocortisone acetate (HyC) treatment of chronically infected mice (5.0 to 7.5 mg per mouse over 3 to 5 days) significantly decreased the size of their granulomas. This diminution may be due to the eosinophil-depleting activity of HyC. Adoptive transfer studies demonstrated that the granuloma suppressor mechanism was HyC-sensitive. A continuing supply of newly developed T lymphocytes appears to be required for the establishment and maintenance of a substantial portion of this immunoregulatory process in chronic infection.

Aging↗
PubMed1980

The eosinophil in the inflammatory response to cercarial challenge of sensitized and chronically infected CBA/J mice.

Sensitized or chronically infected CBA/J mice were challenged percutaneously with cercariae of Schistosoma mansoni. Early inflammatory response was characterized by edema and neutrophil infiltration directed toward penetration tracks; chief pathology associated with schistosomula was localized disruption of epithelial cell relationships, except in areas of desmosomes. By 24 hours eosinophils were the prominent cells in the inflammatory reaction, with large numbers replacing neutrophils in penetration tracks. Extensive local eosinophilia occurred in areas of widespread epidermal destruction and collagen damage. Electron microscopy revealed degranulation of eosinophils in microabscesses and in areas of collagen damage and metabolically active fibroblasts. Eosinophils were rarely observed in contact with schistosomula. No marked difference could be observed between sensitized (but unprotected) mice and chronically infected mice in their response to cercarial challenge; a similar eosinophil response took place whether the mice were partially protected or totally unprotected. The data indicate that although eosinophils may be involved in this protection their presence alone is not sufficient to afford acquired resistance to murine schistosomiasis mansoni.

Animals↗
PubMed1980

Differences in adult Schistosoma mansoni worm burden requirements for the establishment of resistance to reinfection in inbred mice. I. CBA/J and C57BL/6 mice.

Schistosoma mansoni infections of CBA/J and C57BL/6 mice provided the hosts with partial protection against reinfection by S. mansoni cercariae. The level of protection, assayed by perfusion 21-25 days after challenge, varied over the course of infection. After patency the degree of resistance observed in CBA/J mice was related to the adult worm burden harbored by the mice. The same was initially true in C57BL/6 mice. Those C57BL/6 mice which lived until a chronic state of infection were rarely well protected and harbored few female worms. Strain differences were also apparent in that the number of worms required by C57BL/6 mice to establish the same level of protection as CBA/J mice was double that needed by CBA/J mice. Measurements were made of the newly formed egg-induced hepatic granulomas throughout the infection period (up to 30 weeks after infection). The data revealed that although the pattern by which C57BL/6 mice developed maximum granuloma formation and subsequent modulation was identical to that observed in CBA/J mice, C57BL/6 granulomas were consistently half the volume of their counterpart lesions in CBA/J mice.

Animals↗
PubMed1980

Immune responses during human schistosomiasis mansoni. VII. Further analysis of the interactions between patient sera and lymphocytes during in vitro blastogenesis to schistosome antigen preparations.

The lymphocyte blastogenic responses of chronic schistosomiasis mansoni patients were tested in vitro in medium supplemented with either normal human serum or patients' serum (either autologous or third party). As expected, when patients' lymphocytes were cultured in patient sera, many of them (75--78%) displayed reduced responsiveness to schistosome antigens (derived from either the cercariae, adult worms or eggs of Schistosoma mansoni), but not to Candida albicans extract. For decreased blastogenesis to be manifest, a combination of both suppressive sera and suppressible cells was required; however, some patients had nonsuppressible cells and not all sera were suppressive. In an attempt at classification, four categories of patient responsiveness concerning serosuppression are proposed. The categories depend on the suppressive capabilities of patient sera and the response of patient lymphocytes to suppressive sera. By individually testing the capabilities of each patient's lymphocytes and sera in relationship to each antigenic preparation, we were able to assign the majority of patient responses to a given category. It is hoped that by using these categories, a better understanding of the mechanisms concerning serosuppression will be obtained.

Antigens↗
PubMed1979

Immune responses during human schistosomiasis mansoni. VI. In vitro nonspecific suppression of phytohemagglutinin responsiveness induced by exposure to certain schistosomal preparations.

Simultaneous in vitro exposure of human peripheral blood mononuclear cells to phytohemagglutinin-P (PHA) and either soluble schistosomal egg antigenic preparation (SEA) or soluble cercarial antigenic preparation (CAP) obtained from Schistosoma mansoni resulted in decreased responsiveness as compared to exposure to PHA alone. The addition of a soluble adult worm antigenic preparation (SWAP) did not predictably alter PHA responses in this system. The suppression due to in vitro exposure to either SEA or CAP was expressed whether the lymphocyte donors were S. mansoni patients (early infection, chronic, or treated), or uninfected subjects. The degree of suppression was related to the concentration of SEA used, and the timing of exposure. Preexposure to SEA for 3 days before the addition of PHA resulted in more potent suppression. However, a delay in the time of the addition of SEA of 6 and 24 hr after PHA exposure decreased and eliminated, respectively, its suppressive capacity. SEA and CAP were not directly toxic to responding cells, and appeared to exert their nonspecific suppressive influences through T lymphocyte-related mechanisms. It was observed that although these suppressive events could be induced and observed in vitro, the responsiveness of S. mansoni patient lymphocytes to PHA was equal with that of uninfected controls.

Antigens↗
PubMed1979

Partial purification and characterization of Schistosoma mansoni soluble egg antigen with Con A-Sepharose chromatography.

A crude preparation of Schistosoma mansoni soluble egg antigen (SEA) was subjected to affinity chromatography with concanavalin A (Con A) bound to Sepharose 4B. The resulting Con A fractions (bound and unbound) were characterized with sodium dodecyl sulfate (SDS) gel electrophoresis, immunoelectrophoresis, immunodiffusion, and lymphocyte blastogenesis techniques. In the fraction that did not bind to Con A there were at least two distinct antigens, and there were also at least two distinct antigens in the fractions that did bind to Con A. With SDS polyacrylamide gel electrophoresis, at least 20 distinct protein bands (Coomassie blue staining) and three glycoprotein bands (PAS reactive) were present in the unbound fractions from Con A chromatography. The bound fractions separated into at least six distinct glycoproteins with SDS electrophoresis. Although both the bound and unbound fractions contained precipitating antigens, only the bound fractions were capable of eliciting lymphocyte blastogenic responses.

Animals↗
PubMed1979

Immunoaffinity purification of Schistosoma mansoni soluble egg antigens.

Schistosoma mansoni egg antigens were purified from a heterogeneous mixture of soluble egg antigens (crude SEA) with an immunoaffinity column that consisted of the specific anti-SEA antibodies contained in 16-week S. mansoni-infected mouse serum bound to Sepharose 4B. On sodium dodecyl sulfate (SDS) gel electrophoresis, the purified antigen fraction yielded at least eight bands staining with Coomassie blue and at least five bands staining with Coomaisse blue and at least five bands reacting with periodic acid-Schiff (PAS). All of the proteins in the antigenic fraction appear to contain carbohydrate residues. Upon immunoelectrophoresis the antigen yielded four precipitin arcs. The antigenic fraction isolated by means of the immunoaffinity column was then compared to various fractions obtained from concanavalin A (Con A) chromatography of SEA. The results of Ouchterlony immunodiffusion and immunoelectrophoresis indicate that the antigenic fraction isolated by immunoaffinity purification of SEA contains the major antigens found in the fractions obtained from Con A chromatography of SEA. The results of SDS gel electrophoresis indicate that the major PAS-reacting bands of the antigenic fraction isolated by immunoaffinity purification are found in the 3rd peak (bound fraction) resulting from Con A chromatography of SEA, whereas the major Coomaisse blue-staining band in the isolated antigenic fraction is found in the 2nd peak (unbound fraction) from Con A chromatography of SEA.

Animals↗
PubMed1979

Immunoregulation in experimental schistosomiasis: in vitro induction and assay of spleen cell suppressor activity.

Spleen cells from normal CBA/J mice or mice infected with Schistosoma mansoni were exposed for 48 to 72 hr to either concanavalin A (Con A), soluble egg antigen (SEA), or soluble worm antigenic preparation (SWAP), treated with mitomycin C to prevent further DNA synthesis, and admixed with either normal or sensitized syngeneic spleen cells exposed to a concentration gradient of phytohemagglutinin (PHA) or SEA, respectively. Both nonspecific (by Con A) and "antigen-specific" (by SEA and SWAP in infected mice only) induction of suppression was observed when using PHA-induced blastogenesis as the final assay. The number of mice with inducible splenic suppressive activity and the degree of PHA suppression induced by exposure to SEA appeared to decline between 8 and 20 weeks of infection. In contrast, when the response of spleen cells from mice infected for 8 weeks to SEA served as the final assay, strong suppressive activity was induced from the spleen cells of all chronically infected mice (20 weeks of infection). This model permits parallel analysis of the induction of suppressor activity by nonspecific and schistosome antigen-specific signals during the course of this chronic, immunoregulated condition, schistosomiasis mansoni.

Animals↗
PubMed1978

Humoral immune responses in human hepatosplenic schistosomiasis mansoni.

The development of hepatosplenic schistosomiasis in humans cannot always be related to the intensity of infection. A study was designed to identify different humoral immunologic responses to Schistosoma mansoni in patients with and without hepatosplenic disease. Twenty-four patients with active hepatosplenic disease were closely matched for age, sex, and fecal egg counts with twenty-four patients with only intestinal disease. A serum sample from each of these patients was tested for antibodies to the major soluble egg antigen (MSA1) by radioimmunoassay, for total and IgM antibodies to egg and worm antigenic preparations by ELISA, and for its ability to suppress antigen stimulated lymphocyte blastogenesis. No difference was found using these assays between the hepatosplenic and the intestinal schistosomiasis patients.

Adolescent↗