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Biomedical subjects

E A Goidl

Publications and source records attributed to E A Goidl.

At least 37 records · Page 2Linked to original sources
PubMed1983

Spleen cell-mediated suppression of IgG production to a non-parasite antigen during chronic Trypanosoma cruzi infection in mice.

Splenic plaque-forming cell (PFC) responses to TNP-BGG (thymus-dependent) and TNP-Ficoll (thymus-independent) were measured during acute and chronic T. cruzi infections produced in C57BL/10 mice. The number of anti-TNP PFC to both antigens was suppressed as has been shown. Approximately 40% of untreated mice survived acute disease to enter chronic T. cruzi infection characterized by a decrease in parasitemia, a reduction in spleen size, a return to normal of the IgM responses to TNP-BGG and TNP-Ficoll, persistant polyclonal activation, and continued suppression of the IgG responses to TNP-BGG. Mice that were drug-treated during the acute disease had high survival rates and similar immune response patterns, ie., suppressed IgG PFC responses to TNP-BGG and normal IgM PFC responses to TNP-BGG and TNP-Ficoll. The selective suppression of the IgG response was transferred to nonirradiated syngeneic recipients by Thy-1.2-positive cells present in the spleens of chronically infected mice. These observations may be interpreted to suggest the persistence of nonspecific suppressor T cells during chronic T. cruzi infections.

Animals↗
PubMed1981

Effect of age on the induction of autoantibodies.

Three experimental models were used to compare the ease of inducing autoantibodies in young and old mice. Autoantibody to thyroglobulin (Tg) induced by immunization with cross-reactive xenogeneic Tg in Freund's complete adjuvant and autoerythrocyte antibody induced by the injection of xenogeneic erythrocytes were studied in C57Bl/6 and BALB/c male mice. In both strains, the anti-thyroglobulin antibody response to lower doses of xenogeneic Tg was significantly lower in old as compared with young animals. There were no detectable differences in incidence or strength of the direct Coombs' test following the administration of rat erythrocytes to old or young animals. In contrast, anti-mouse erythrocyte autoantibody-secreting spleen cells, generated in culture and assayed on bromelin-treated mouse erythrocytes, were more numerous in cultures of spleen cells from old as compared with young mice. These results suggest that the regulation of the autoantibody production which is stimulated by cross-reactive antigens is under different control from the spontaneous age-related increase in autoantibodies.

Aging↗
PubMed1980

Production of auto-anti-idiotypic antibody during the normal immune response. IV. Studies of the primary and secondary responses to thymus-dependent and -independent antigens.

We have previously shown that hapten-augmentable plaque-forming cells are cells whose secretion of antibody is inhibited by the binding of auto-anti-idiotype antibody to cell surface antigen receptors. Using hapten augmentation of plaque formation, it was shown in the present report that auto-anti-idiotype antibodies are produced during the primary and secondary responses to both thymus-dependent und thymus-independent antigens. In the secondary response to the T-independent antigen trinitrophenylated Ficoll, the rate of appearance of auto-anti-idiotype antibody was faster, and the number of hapten-augmentable plaques was greater than in the primary response suggesting an anamnestic auto-anti-idiotype response. With the T-dependent antigen, trinitrophenylated bovine gamma-globulin, the kinetics and magnitude of the auto-anti-idiotypic antibody response were relatively similar in the primary and secondary responses. However, a lower concentration of hapten was required to reveal the hapten-augmentable plaques in the secondary response. This is in keeping with the usual finding that secondary antibody to T-dependent antigens is of very high affinity. Both direct and indirect hapten-augmentable plaque-forming cells were detected suggesting that the secretion of both IgM and IgG antibodies is regulated by auto-anti-idiotype antibodies. The data are consistent with a role for auto-anti-idiotype antibody in the normal down-regulation of the immune response as suggested by Jerne's network hypothesis.

Animals↗
PubMed1980

Ontogeny of B lymphocyte function. VIII. Failure of thymus cells from aged donors to induce the functional maturation of B lymphocytes from immature donors.

The role of thymus cells in mediating a step in the ontogeny of the capacity of the B cell population to produce a heterogeneous, high-affinity, primary, plaque-forming cell (PFC) response was further investigated. It was shown that the thymus acquires the capacity to facilitate this step in B cell differentiation between 3 and 4 weeks of age in C57BL/6 mice. This corresponds to the age at which te splenic B cell population of these mice naturally acquires the capacity to produce high-affinity PFC. The differentiation of the B cell population. It was further shown that regulates this step in the cells to facilitate the maturation of B cell population. It was further shown that the ability of thymus cells to facilitate the maturation of the B cell population decreases with age and is already markedly reduced in 30-week-old, long-lived, C57BL/6 mice. A qualitative or quantitative decrease in thymic function may thus be responsible for age-related changes in the function of the B cell population.

Aging↗
PubMed1980

Production of auto-anti-idiotypic antibody during the normal immune response: changes in the auto-anti-idiotypic antibody response and the idiotype repertoire associated with aging.

Hapten-augmentable plaque-forming cells (PFC) are cells whose secretion of antibody is specifically inhibited by surface-bound auto-anti-iodotype antibody that can be displaced by hapten. This study showed that the percentage of hapten-augmentable PFC present in mice during the primary response to trinitrophenylated Ficoll (TNP-F) increases with age. The data suggest that there is a relative increase in the auto-anti-idiotypic antibody response with age and therefore a greater down-regulation of antibody production. The effect of age on idiotype expression was also studied. Hapten-reversible inhibition of plaque formation was used as an assay for anti-inhibition of plaque formation was used as an assay for anti-idiotype antibody and idiotype-bearing antibody-secreting cells. Sera from aged (21- to 22-month-old) C57BL/6 mice immunized with TNP-F significantly inhibited plaque formation, in a hapten-reversible manner, by spleen cells from 81% of TNP-F-immunized aged mice. However, these sera inhibited plaque formation by cells from only 50% of similarly immunized young adult (6- to 8-week-old) mice and 20% of immature (3- to 4-week-old) syngeneic mice. Similarly, sera from TNP-F-immunized young adult or immature mice inhibited formation of plaques by cells from immunized donors of the same age as the mice from whom the serum was obtained, but only rarely inhibited plaque formation by cells from mice of other age groups. The data thus suggest that the repertoire of TNP-specific idiotypes that are produced in response to TNP-F varies with age in syngeneic mice.

Aging↗
PubMed1979

Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. III. Absence in nu/nu mice: evidence for T-cell dependence of the anti-idiotypic-antibody response.

Although athymic mice make an excellent immune response to the thymus-independent antigen trinitrophenyl-lys-Ficoll (TNP-F), nude mice of AKR/J and BALB/c strains lack the anti-idiotypic response that occurs in euthymic mice of both of these strains within the first 1--2 wk after injection of more TNP-F. Anti-idiotypic antibody-blocked (hapten-augmentable) anti-TNP splenic plaque-forming cells (PFC) do not occur at any time and serum anti-idiotypic antibody is absent in both congenitally athymic mice, and thymectomized, irradiated, bone marrow-reconstituted mice. Nevertheless, nu/nu mice do have PFC which can be inhibited by exposure to anti-idiotypic antibody produced in +/+ mice. As a consequence of the failure to produce anti-idiotypic antibodies, the anti-TNP PFC response is athymic as compared to euthymic mice is of greater magnitude, declines less precipitously, and shows an increase rather than a decrease in affinity between days 4 and 7 after antigen injection. It is concluded that the anti-idiotypic antibody response is thymus dependent and that athymic mice lack a helper cell required for the induction of anti-idiotypic antibodies.

Animals↗
PubMed1979

Production of auto-anti-idiotypic antibody during the normal immune response to TNP-ficoll. I. Occurrence in AKR/J and BALB/c mice of hapten-augmentable, anti-TNP plaque-forming cells and their accelerated appearance in recipients of immune spleen cells.

Attempts were made to elucidate the cause of the downward regulation of the splenic plaque-forming cell (PFC) response in AKR/J and BALB/c mice between days 4 and 7 after a single intravenous injection of 2,4,6,trinitrophenyl- lys-Ficoll(TNP-F). AKR/J spleen cells, taken 7 d after injection of TNP-F, were transferred, together with TNP-F, into normal AKR/J mice. The day-3 or - 4 PFC response of the recipients was much lower than that of recipients of normal cells. However, the suppression was only apparent because the presence of 10(-8)-10(-7) M 2,4,6-trinitrophenyl-epsilon-amino-n-caproic acid (TNP- EACA) (or 10(-7)-10(-6) M 2,4,-dinitrophenyl-epsilon-amino-n-caproic acid) in the PFC assay caused a dramatic increase in observed PFC, averaging 298 percent on day 3 and 122 percent on day 4. Recipients of normal cells showed no such hapten-augmentable PFC. T-depleted immune spleen cells did not cause any apparent suppression of the response to TNP-F, but hapten-augmentable PFC in recipient spleens were again prevalent. Suppression of the PFC response, as well as hapten-augmentable PFC, were seen after transfer of immune serum. It was postulated that hapten augmentation of PFC was caused by displacement of auto-anti-idiotypic antibody from the surface of blocked antibody- synthesizing cells. Further studies showed that such hapten-augmentable PFC occurred in the spleens of a large percentage of both AKR/J and BALB/c mice examined after day 4 of the primary response to TNP-F. Thus, it was hypothesized that the downward regulation of the magnitude and, possibly, also of the heterogeneity of the splenic-PFC response was due to an auto-antibody response to one or more major idiotypes of the anti-TNP response.

Animals↗
PubMed1979

Production of auto-anti-idiotypic antibody during the normal immune response to TNP-Ficoll. II. Hapten-reversible inhibition of anti-TNP plaque-forming cells by immune serum as an assay for auto-anti-idiotypic antibody.

Sera taken from AKR/J mice 7 d after the intravenous injection of 2,4,6-trinitrophenyl-lys-Ficoll (TNP-F) caused a specific inhibition of anti- trinitrophenol (TNP) plaque-forming cells (PFC) in vitro. This inhibition was reversed by the incorporation of 10(-8)-10(-7) M 2,4,6-trinitrophenyl- epsilon-amino-n-caproic acid (TNP-EACA) into the agar during the PFC assay. The factor responsible for the hapten-reversible PFC inhibition was removed from serum by passage through an anti-immunoglobulin column or through a 2,4,-dinitrophenyl-human-serum-albumin-bromoacetylcellulose plus anti-TNP- antibody column, but not by DNP-HSA-BAC alone. It was concluded that this immunoglobulin-like substance, lacking anti-TNP activity but reacting with anti-TNP antibody of AKR/J origin, was most likely an auto-anti-idiotypie antibody that had been produced during the normal course of the response of AKR/J mice to TNP-F. Pools of anti-idiotypic-antibody-containing antisera inhibited anti-TNP plaque formation to varying degrees when tested on d-4 PFC from different mice of the same inbred strain, suggesting a variability in idiotype expression. 4 d after transfer of immune (7 d after 10 mug TNP-F, administered intravenously) AKR/J spleen cells plus 10 mug TNP-F into syngeneic mice, the number of PFC detectable in the recipients' spleens could be markedly augmented by the inclusion of TNP-EACA in the agar during the PFC assay. Incubation of spleen cells containing such hapten-augmentable PFC with TNP- EACA yielded a factor in the supernate that caused a specific, in vitro, hapten-reversible inhibition of anti-TNP PFC. Studies with immunoadsorbents indicated that this PFC-inhibiting factor was antigenically immunoglobulin- like, lacked anti-TNP-antibody activity, but reacted with anti-TNP antibody of AKR/J origin. The results are consistent with the view that this PFC inhibitor is auto-anti-idiotypic antibody that is involved in the normal regulation of the immune response. It is proposed that hapten-reversible inhibition of plaque formation can be employed as an assay for anti-idiotypic antibody and the conditions for such an assay are described. It is further proposed that the detection of hapten-augmentable PFC suggests the presence of auto-anti-idiotypic antibody.

Animals↗
PubMed1978

Adult murine T cells activated in vitro by alpha-fetoprotein and naturally occurring T cells in newborn mice: identity in function and cell surface differentiation antigens.

Murine alpha-fetoprotein (alphaFP) has been shown to suppress T cell-dependent antibody responses in vitro but not T cell-independent responses. Our earlier preliminary findings indicated that such inhibitory effects are mediated via activated T cells. In this study, using alphaFP as the inducing agent, we have analyzed cells generated in vitro from adult spleen cells with regard to function and surface markers and compared the cells to the naturally occurring splenic T cells of newborn mice, in which there are high intrinsic concentrations of alphaFP. Both types of T lymphocytes were found to effectively inhibit T cell-dependent antibody responses in vitro but not T cell-independent responses. Moreover, both groups of T cells were found to express the identical differentiation antigen phenotype,Ly 1 + 2-. Thus alphaFP-induced inhibitory T cells from adults could be shown to have the same functional properties and Ly phenotype as splenic T lymphocytes from newborn mice. These findings support the concept that alphaFP might function as an important immunoregulatory agent in vivo during ontogenetic development.

Age Factors↗
PubMed1976

Immunological studies of aging. II. Loss of IgG and high avidity plaque-forming cells and increased suppressor cell activity in aging mice.

The magnitude and heterogeneity of the immune response to dinitrophenylated bovine gamma globulin was measured in aged and young mice at a cellular level using an inhibition of plaque-forming cell assay. The primary and secondary responses of 24-mo-old mice were markedly depressed in magnitude and restricted in avidity for the DNP determinant when compared to 2-mo-old animals. Bacterial lipopolysaccharide given at the time of immunization increased the restriction in heterogeneity seen in 12- and 24-mo-old mice. Indirect PFCs were more severely depressed than direct PFCs in 24-mo-old mice. Syngeneic, lethally irradiated, 2-mo-old mice reconstituted with aged spleen cells exhibit the depressed and restricted response to DNP-BGG seen in old mice. When 10(8) young thymus cells were given together with old spleen cells the heterogeneity of the response was increased. When 2-mo- and 24-mo-old spleen cells were transferred together into young recipients the magnitude of the response to the young spleen cells markedly reduced. Thus, there appears to be a loss of thymic-helper cells and an increase in suppressor activity in aged animals.

Aging↗
PubMed1976

Ontogeny of B-lymphocyte function. II. Ability of endotoxin to increase the heterogeneity of affinity of the immune response of B lymphocytes from fetal mice.

The ontogeny of the functional capacity of B lymphocytes to generate a heterogeneous response to a haptenic determinant was studied by cell transfer techniques in LAF1 mice. Fetal liver, as a source of B lymphocytes, was transferred into adult, syngeneic, irradiated animals. All recipients received excess adult thymus cells so that T-cell activity did not limit the response and were immunized with DNP-BGG. The heterogeneity of avidity of their anti-DNP PFC response was assayed by hapten inhibition of plaque formation. Animals reconstituted with B lymphocytes from fetal donors produced a response that is highly restricted with respect to heterogeneity of affinity. Transfer studies using multiple fetal donors or mixtures of adult and neonatal cells for reconstitution suggest that the restriction in heterogeneity is not the consequence of suppressor T-lymphocyte activity. With animals reconstituted with B cells from day 16 or older fetal donors, injection of LPS together with antigen converted the response to a heterogeneous "adult-type" response. With animals reconstituted with B lymphocytes from day 14 fetal liver DxSO4, but not LPS, could convert the response to a highly heterogeneous one. Animals reconstituted with day 14 or 16 fetal liver as source of B lymphocytes were capable of producing a heterogeneous secondary response despite the fact that their primary response was of restricted heterogeneity. This implies the selection of high affinity B-memory cells, in the absence of high affinity PFC during the primary response with fetal B lymphocytes. Animals reconstituted with day 14 or 16 fetal liver produce only direct PFC, while animals reconstituted with day 18 fetal liver produce both direct and indirect PFC. Three differentiation events have therefore been defined in the functional development of B lymphocytes: (a) between day 14 and day 16 of fetal life they acquire responsiveness to LPS; (B) BETWEEN DAY 16 AND 18 OF FETAL DEVELOPMENT THEY ACQUire the capacity to produce indirect PFC; (C) between day 7 and 10 after birth they acquire the capacity to give a heterogeneous response after normal immunization. In addition, it was shown that LAF1 mice already have all of the information required to produce an "adult-type" heterogeneous anti-DNP response at day 14 of fetal life.

Age Factors↗
PubMed1975

Determination of antibody avidity at the cellular level by the plaque inhibition technique: effect of valence of the inhibitor.

Inhibition of plaque formation by multivalent and univalent ligands was compared as an assay of avidity of antibody produced by PFC. Multivalent ligands are much more effective as inhibitors and their use tends to impart an appearance of lack of heterogeneity and high avidity to the PFC populations being studied. It is thus probably generally advisable to employ univalent ligands in such studies.

Aminocaproates↗