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A H Coons

Publications and source records attributed to A H Coons.

At least 19 recordsLinked to original sources
PubMed1978

Effect of colchicine on the antibody response. I. Enhancement of antibody formation in mice.

Colchicine (CC) enhances the antibody response in mice to protein antigens, like diphtheria toxoid and human gamma globulin, as well as to the 2,4,6-trinitrophenyl hapten. Maximal enhancement was observed when CC was administered to animals on the same day as the injection of antigen. The optimal dose of CC was in the range of 1.0-1.5 mg/kg body weight. The enhanced antibody formation was evident from elevated circulating antibody titers and from an increased number of antibody plaque-forming cells (PFC) of the spleen. The circulating antibody titer of CC-treated animals was higher than that of control animals by a factor of about 3-7 in the primary response, and by a factor of at least 15 in the secondary response. In terms of the number of antibody forming cells, CC enhanced the primary PFC response by approximately equal to 100%, and the secondary PFC response by as high as fivefold. The enhancing effect of CC seemed to be related to its mitosis-blocking capacity since (a) vinblastine another antimitotic drug, was found to be as effective as CC and (b) lumicolchicine, the non-anti-mitotic structural isomer of CC, was ineffective in potentiating antibody responses. The critical timing in the administration of CC on the same day as antigen suggests that most likely, the mitotic poison was acting on antigen-stimulated early dividing suppressor cells.

Animals↗
PubMed1978

Effect of colchicine on the antibody response. II. Demonstration of the inactivation of suppressor cell activities by colchicine.

The simultaneous administration of colchicine (CC) with a T-independent antigen, e.g. 2,4,6-trinitrophenyl-keyhold limpet hemocyanin-Sepharose, to intact animals effectively enhanced their hapten-specific plaque-forming cell (PFC) response. However, in congenitally athymic nude mice in which T-cell regulation was absent, CC was ineffective in producing enhancement. These observations suggest that the target cell acted upon by CC is most likely thymus-derived. Furthermore, the injection of CC with the co-polymer of L-glutamic acid50-L-tyrosine50 (GT) abolished GT-specific suppression of the PFC response to GT-methylated bovine serum albumin. Spleen cells from CC-treated and GT-primed hosts could no longer transfer suppressive activity to normal recipients. These results provide evidence that CC is capable of inactivating or eliminating suppressor cells or their precursors. Thus, CC-induced enhancement of the antibody response may be explained, at least in part, by its antimitotic, and hence lethal effect on dividing suppressor T cells.

Animals↗
PubMed1978

Complement-dependent stimulation of normal lymphocytes by immune complexes.

Normal rabbit lymphocytes were stimulated to proliferate in vitro by antibody-antigen complexes. Stimulation was dependent upon C activity. Heat-inactivation or zymosan-treatment of the serum used in culture caused a 75 to 100% loss of responsiveness to the complexes. Serum-free culture or cultures with less than 1% serum supported only low levels of stimulation, but responsiveness reappeared proportionally with increased serum concentration. The low level dose-dependent responses seen in the absence of active C may have been due to C carried over with the cells or to stimulation independent of C. Aggregated rabbit gamma-globulin tested over a broad dose range failed to stimulate normal lymphocytes more than minimally whether or not C was present. Stimulation with immune complexes was sustained by C4-deficient guinea pig serum, indicating participation of the alternative C pathway. Normal rabbit lymphocytes from peripheral blood, bone marrow, spleen, and lymph node proliferated in response to rabbit antibody-antigen complexes. Normal thymocytes were consistently unresponsive to the complexes.

Animals↗
PubMed1976

Characterization of T and B antigen-binding cells for beta-galactosidase. II. T antigen-binding cells.

The results reported in this paper suggest that the specific Z-binding cells of the normal mouse include a large portion of T lymphocytes. Depletion of T cells with anti-theta serum and cortisone indicates that the majority of the ZBC of the thymus, which occur at frequencies of about 150/10(6), are indeed T cells. Similar treatment of spleen cells suggests that approximately half the binding cells in that organ are contributed by the T lymphocyte population. T-and B-enriched populations obtained from the spleen by using differential adherence to nylon wool contained equal numbers of ZBC and bound equivalent amounts of the antigen. Hence, there appears to be a high frequency of T lymphocytes that can be shown to bind beta-galactosidase specifically in both the thymus and spleen of normal mice.

Animals↗
PubMed1976

Characterization of T and B antigen-binding cells for beta-galactosidase. III. Independence of antigen-binding cells in normal animals from antigenic stimulation.

Antigen-binding cells to beta-galactosidase were enumerated in thymus and spleen of mice of different ages and found to remain at a constant frequency throughout life. Thymic beta-galactosidase-binding cells (ZBCs),6 representing T-binding cells, showed no appreciable fluctuation, whereas splenic ZBCs, a mixture of T- and B-binding cells, were slightly depressed at birth but found at normal frequencies by 1 week of age. In addition, germfree mice, both within the 1st week after birth and after maturity, had nearly as many binding cells as did conventionally reared age-matched mice. These results considered together suggest that the ability of cells of both T and B origin to recognize antigen, as revealed by their ability to bind beta-galactosidase, arise independently of specific or nonspecific antigenic stimulation, as part of the normal ontogenic sequence of steps of differentiation. This is consistent with the theory of clonal precommitment of T and B cells.

Aging↗
PubMed1976

Characterization of T and B antigen-binding cells for beta-galactosidase. I. beta-galactosidase-binding cells in the thymus and spleen of normal mice.

The results reported in this paper demonstrate that the enumeration of cells binding beta-galactosidase (Z) as an antigen, revealed by subsequent substrate hydrolysis, is an excellent method for the detection and study of antigen-binding cells (ZBC). The binding found is specific and is restricted to a small number of lymphocytes that bind a large number of Z molecules via surface receptors. Such ZBC were found at mean frequencies of 150 per 10(6) in the thymus and 200 to 300 per 10(6) in the spleen. The binding cells of both organs were heterogenous with individual ZBC binding from 10(5) to 10(6) molecules of enzyme as determined by substrate hydrolysis, although this might well be an overestimate of the number of actual receptors. The profiles for the frequency of ZBC binding different numbers of molecules were nearly identical for thymus and spleen, in contrast to descriptions of the binding of many other antigens. Receptors responsible for Z binding appear to be superficially located on the cell since they are trypsin-sensitive to a large extent and are not increased by fixation.

Animals↗
PubMed1974

Specific heterologous enhancement of immune responses. VI. Partial purification of a nonspecific enhancing factor from supernates of allogeneically stimulated human lymphocyte cell lines.

The mixing of two histoincompatible human lymphocyte cell lines generated the release of a soluble factor which was capable of nonspecifically enhancing the in vitro immune response of normal mouse spleen cells against sheep erythrocytes. When active supernates were subjected to exclusion chromatography on Sephadex G-150 and BioGel P-150, the active principle eluted with molecules of approximately 35,000 mol wt. Column aliquots from similarly treated supernates from independent cultures of each lymphoid cell line were inactive. The human enhancing factor was concentrated and purified by ammonium sulfate fractionation, followed by Sephadex gel filtration and polyacrylamide gel electrophoresis.

Animals↗
PubMed1973

Studies on membrane-bound receptors for antigen. Preparation of populations of receptor-depleted lymphocytes.

THE EFFECT OF POLYADENYLIC: polyundylic acid complexes (poly A:U) on the amount of antibody on the surface of various populations of mouse lymphoid cells has been investigated by means of a sensitive measure of such activity-the binding by primed cell populations of beta-galactosidase (betaGZ) as an antigen. The sensitivity derives from the liberation of fluorescein from an artificial substrate, fluorescein-di-beta-galactopyranoside (FDbetaG). After incubation with 100 ng/ml of poly A:U, only 40% of the cells previously showing antigen-binding were still active. The optimum range of activity lay between 0.01-1.0 microg/ml poly A:U. Such cells showed increased RNA and protein synthesis as indicated by [(3)H]uridine and [(14)C]amino acid incorporation. The polynucleotide effect was abolished by incubation of the cells with sodium azide or iodoacetate, but not by puromycin. When the proteins on the cell surface were labeled by (125)I, poly A:U caused their release into the medium. Reports by others that the enhancing effect of polynucleotides on the immune response involves the adenylcyclase system are consistent with the finding reported here that reduction of binding by dibutryl 5'-cyclic monophosphoric acid (cAMP) and poly A:U were parallel in extent, and that theophylline and poly A:U acted synergistically in suboptimal concentrations of each.

Amino Acids↗
PubMed1972

Specific heterologous enhancement of immune responses. IV. Specific generation of a thymus-derived enhancing factor.

In short-term cultures of thymocytes from tetanus toxoid-immunized mice, the addition of 1 ng of toxoid generated the release of a soluble factor which was capable of enhancing the immune response to a heterologous immunogen. The addition of supernatants from such cultures to assay cultures of sheep erythrocyte-stimulated normal spleen cells produced a significant augmentation of the hemolytic plaque response. Culture fluid from similar cultures of normal thymocytes or primed thymocytes cultured without the priming antigen were inactive. The enhancing factor was nondialyzable, heat stable (56 degrees C, 30 min), resistant to DNAse and RNAse, but was inactivated by protease. A factor produced by specifically stimulated primed spleen cells had similar characteristics. In toxoid-stimulated, mixed cell cultures containing primed thymocytes or spleen cells and normal spleen cells, tenfold fewer thymocytes than spleen cells were needed to produce a comparable degree of enhancement of the anti-sheep erythrocyte plaque-forming cell response.

Animals↗
PubMed1971

Specific heterologous enhancement of immune responses.

In suspension cultures of mouse spleen cells, the addition of small amounts (1-100 ng) of a heterologous antigen to which the donor mice had been primed significantly increased the number of anti-sheep erythrocyte plaques appearing after stimulation with sheep erythrocytes. A similar addition to identical cultures from unprimed donors produced a small depression in the number of such plaques.

Animals↗