Biomedical subjects

G A Silverman

Publications and source records attributed to G A Silverman.

59 records · Page 4Linked to original sources

PubMed1983

Enterically induced regulation of systemic immune responses. I. Lymphoproliferative responses in mice suppressed by ingested antigen.

The effects of local antigenic exposure on the responsiveness of systemic T cells were evaluated after C3H mice were given drinking water containing 6% bovine serum albumin (BSA) for 10 days and challenged sc with 1.0 mg BSA in adjuvant 28 days after the initiation of antigen feeding. During the first 28 days, no evidence of in vitro antigen-induced proliferation [( 3H]thymidine incorporation) was detected in whole lymphocyte populations from the peripheral lymph nodes (PLN), spleen, or mesenteric nodes. In contrast, PLN cells treated with anti-Lyt-1 plus complement (C) had a significant proliferative response only if the cells were obtained during the first 6 days of antigen ingestion. Lymphoid cells from the same animals, treated with anti-Lyt-2 and C, did not respond to antigen. Two or 4 days after the injection, given on day 28, whole PLN cell populations from antigen-fed mice showed proliferation. No response was observed with PLN cells obtained 8 days after injection. Shortening the interval between the initiation of feeding and parenteral challenge partially restored proliferative responses detected 8 days after injection. Cultures prepared 4 days after simultaneous oral and parenteral antigenic exposure showed proliferation equal to or greater than cultures from mice that received only the injection. These data show that systemic T cell responsiveness is not eliminated by ingestion of soluble antigen, but rather is modulated in a manner previously detected in the humoral immune system.

Administration, Oral↗

PubMed1983

Enterically induced regulation of systemic immune responses. II. Suppression of proliferating T cells by an Lyt-1+, 2- T effector cell.

Peripheral lymph node cells from C3H mice that were fed and injected with bovine serum albumin (REG cells) demonstrate an impaired proliferative response to antigenic stimulation in vitro compared to cells from mice only injected with BSA. To determine whether suppressor cells contributed to this enterically induced impairment of systemic T cell responses, REG cells were pretreated with various monoclonal antibodies and complement (C), and were then co-cultured with antigen-reactive indicator T cells (IND) from parenterally immunized mice. Proliferation of IND cells [( 3H]thymidine uptake) was suppressed only if REG cells were treated with anti-Lyt-2 and C before co-culture. The ability of anti-Lyt-1 plus anti-Lyt-2 and C treatment to abrogate suppression suggested that the suppressor effect was due to an Lyt-1+, 2- REG cell. Suppression was independent of Lyt-2+ IND cells, and was observed at different antigen concentrations, cultivation times, and cell densities. The cells responsible for suppressor activity were radiosensitive, nylon wool nonadherent, and antigen specific. These data suggest that an Lyt-1+, 2- T cell could be an important component in mediating enterically induced regulation of systemic T cell responses.

Animals↗

PubMed1982

Systemic antibody responses of different species following ingestion of soluble protein antigens.

Following ingestion of bovine serum albumin (BSA), human infants and rabbits synthesize circulating anti-BSA. Using a similar protocol, the serum antibody response was examined in C3H mice offered 0.1, 1.0 or 6.0% BSA for 10 or 56 days. Sera from these animals contained similar amounts of antigen, but anti-BSA was undetectable. Half the animals in each group were subsequently injected i.v. with 50.0 mg BSA. Mice fed 1.0 or 6.0% BSA were unresponsive to this challenge, but animals fed 0.1% BSA responded comparably to i.v. immunized, non-fed controls. The remaining animals in each group were injected s.c. with 1.0 mg BSA in adjuvant. Most of these mice produced circulating anti-BSA. However, these responses were significantly reduced relative to s.c. immunized, non-fed controls. Hyporesponsiveness again was least after 0.1% BSA ingestion. CF1 mice and BN, HCR and HCS rats fed 0.1% BSA for 56 days also did not produce circulating antibodies during ingestion, and almost all were hyporesponsive after parenteral challenge. Suppression of specific antibody responses also was observed in C3H mice fed and challenged with diphtheria toxoid. The data suggest that under identical experimental conditions, ingestion of soluble protein antigens induces a state of systemic hyporesponsiveness in mice and rats in contrast to the systemic immunity demonstrated in human neonates and adult rabbits.

Administration, Oral↗

PubMed1979

Inhibition of spontaneous AKR leukemia by multiple inoculations of Corynebacterium parvum.

In previous studies we have shown that AKR mice could be protected from spontaneous leukemia by specific immunotherapy in combination with splenectomy. In this experiment we investigated the effects of nonspecific immunotherapy with C. parvum in a similar regimen. It was found that bi-weekly, ip inoculations of 0.7 mg of C. parvum could significantly protect AKR mice from spontaneous tumors, and that splenectomy could not modify this effect. Thus, the spleen does not appear to play a determinant role in mediating the protective effects of C. parvum, as had been suggested in other systems.

Animals↗

PubMedDate not supplied

Characterization of monoclonal antibodies directed against squamous cell carcinoma antigens: report of the TD-10 Workshop.

Thirteen monoclonal antibodies directed against squamous cell carcinoma antigens (SCCA1 and SCCA2) were obtained from five international collaborating laboratories participating in the ISOBM TD-10 Workshop. Native and recombinant forms of SCCA were used in a wide variety of approaches to determine the reactivity and specificity of these antibodies. Based on reactivity, the antibodies could be divided into three groups: the SCCA1-reactive group containing those that reacted only with recombinant SCCA1 (rSCCA1) and native SCCA1 (nSCCA1) antigens, the SCCA2-reactive group containing those that reacted only with recombinant SCCA2 (rSCCA2), and the pan-reactive group containing those antibodies that reacted with rSCCA1, nSCCA1, and rSCCA2. Binding to radioiodinated rSCCA1 showed that all reactive antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Binding to labelled rSCCA2 demonstrated that five antibodies were of a high affinity (K(d) <2 x 10(-9) mol/l). Antibody reactivity on Western blots was tested with nonreduced and reduced native and recombinant SCCA1 and SCCA2. In general, these findings showed that reduction had little effect on binding to SCCA1, but often a strong effect on the binding to SCCA2. Binding of antibodies to rSCCA1 and rSCCA2 in complexes with cathepsin L and G, respectively, was used to assist in the localization of epitope regions in enzyme-complexed SCCA. Cross-inhibition experiments showed that SCCA1-reactive antibodies represent two different epitope groups, and this is supported by their ability to make SCCA1-specific assays by combining antibodies from the two epitope groups. The SCCA2-reactive group represents two related antibodies and one unique as seen in cross-inhibition, but they do not form successful assay combinations. Classification of the pan-reactive antibodies is more difficult, as some epitope groups differ when results from rSCCA1 are compared with rSCCA2 as the target. However, two antibodies are outstanding, SCC107 and SCC113, as they are high-affinity antibodies which react equally well with free and protease complexes of SCCA1 and SCCA2. The precise location of epitopes was further studied using sequential overlapping peptides and homology modelling. The findings from this workshop strongly indicate that the recombinant antigens (rSCCA1 and rSCCA2) are very similar in epitope structure to the native counterparts in saliva, and squamous epithelium from normal and cancer tissues. Therefore, it is reasonable to conclude that the specificities found are reliable and have application for antibody measurement of all forms of squamous cell carcinoma in serum except SCCA2 in complex with its protease.

Antibodies, Monoclonal↗