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D H Katz

Publications and source records attributed to D H Katz.

At least 19 recordsLinked to original sources
PubMed1979

Suppression of hapten-specific delayed-type hypersensitivity responses in mice by idiotype-specific suppressor T cells after administration of anti-idiotypic antibodies.

Delayed-type hypersensitivity (DTH) responses specific for the phosphorylcholine (PC) hapten were induced in BALB/c mice by immunization with syngeneic peritoneal exudate cells (PEC) coupled with diazotized phenyl-phosphoryl-choline. PC-specific DTH responses were elicited in such immunized mice after footpad challenge with PC-derivatized syngeneic spleen cells. Moreover, PC-immune lymph node cells could passively transfer PC-specific DTH responses to naive BALB/c mice and it was possible to demonstrate that the cells responsible for such passively transferred responses were T lymphocytes. Because the T-15 idiotypic determinant displayed on the TEPC-15 PC-binding myeloma protein is known to be a dominant idiotype associated with anti-PC antibody responses in BALB/c mice, an analysis was made of the effects of anti-T-15 idiotypic antibodies on the induction and expression of murine PC-specific DTH responses. Repeated injections of anti-T-15 idiotypic antiserum, raised in A/J mice by immunization with TEPC-15 myeloma protein, into recipient BALB/c mice both immediately before and after sensitization with PC-PEC virtually abolished the development of PC-specific DTH responses. Although administration of anti-T-15 antiserum effectively inhibited the induction phase of PC-specific DTH responses, these anti-idiotypic antibodies had no suppressive activity at the effector phase of these responses. The inhibition observed with anti-T-15 antibodies was highly specific for the PC hapten, and for PC-specific DTH responses of BALB/c but not A/J mice. Studies were conducted to address the possibility that anti-Id treatment induced suppressor T lymphocytes capable of specifically inhibiting the activity of PC-specific T cells participating in DTH responses. The results demonstrate that idiotype-specific suppressor T cells are, indeed, induced by treatment with anti-Id; moreover, such suppressor T cells, once induced, are highly effective in abrogating both the induction and the effector phases of PC-specific T cell-mediated DTH responses in BALB/c mice.

Animals↗
PubMed1979

Adaptive differentiation of murine lymphocytes. IV (Responder x nonresponder) F1 T cells can be taught to preferentially help nonresponder, rather than responder, B cells.

Responses to the synthetic terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) in the mouse are controlled by H-2-1inked Ir-GLTgenes. (Responder x nonresponder) F(1) hybrid mice, themselves phenotypic responders, can be primed with GLT to develop specific helper cells capable of interacting with 2,4-dinitrophenyl hapten (DNP)-primed F(1) B cells in response to DNP-GLT. Unlike the indiscriminant ability of F(1) helper T cells for conventional antigens (i.e. not Ir gene-controlled), which can help B cells of either parental type (as well as F(1)) equally well, GLT-primed F(1) T cells can only provide help under normal circumstances for B lymphocytes of responder parent origin; they are unable to communicate effectively with nonresponder parental B cells (1, and the present studies). The present studies reveal, however, that the induction of a parental cell-induced allogeneic effect during priming of F(1) mice to GLT actually dictates the direction of cooperating preference that will be displayed by such F(1) helper cells for B cells of one parental type or the other. Thus, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by parental BALB/c cells, develop into effective helpers for nonresponder A/J B cells, but fail to develop effective helpers for responder BALB/c B cells, and vice-versa. In contrast, F(1) T cells, primed to GLT under the influence of an allogeneic effect induced by either parental type, display significantly enhanced levels of helper activity for B cells derived from F(1) donors. These results are interpreted to reflect the existence of two interdependent events provoked by the allogeneic effect: one event augments the differentiation of GLT-specific helper T cells belonging to the subset corresponding to the opposite parental type; this would explain the development of increased helper activity provided to partner B cells of opposite parental type (as well as of F(1) origin). The second event, we postulate, involves the production of responses against the receptors which normally self-recognize native cell interaction determinants; this form of anti-idiotype response is restricted against self- recognizing receptors of the same parental type used for induction of the allogeneic effect, hence explaining diminished helper activity of such F(1) cells for partner B lymphocytes of corresponding parental type.

Animals↗
PubMed1979

Adaptive differentiation of murine lymphocytes. II. The thymic microenvironment does not restrict the cooperative partner cell preference of helper T cells differentiating in F1 leads to F1 thymic chimeras.

The cooperating preference of helper T cells originating from F1 bone marrow, but differentiating in adult thymectomized, lethally irradiated F1 recipients reconstituted with either f1 or homozygous parental thymus grafts was investigated. Cooperating preference was assayed by determining the levels of helper activity provided by antigen-primed T cells derived from such thymic chimeras for hapten-primed B lymphocytes obtained from conventional F1 or parental donors in adoptive secondary antibody responses in vivo. The results of these analyses revealed a tendency of helper T cells derived from parental thymic chimeras to provide better help for B cells of the same parental type corresponding to the origin of the thymus graft than for the opposite parent. Such preference was, however, only marginal and rarely were differences in levels of helper activity provided to the respective parental types statistically significant. Moreover, this marginal preference, when observed, pertained only to responses of the IgG class; no concordant preference in providing helper activity for IgE antibody responses was observed even with the same populations of thymic chimera helper T cells. Finally, in no instance was there any evidence of restriction in the classical sense of presence versus absence of help as we have routinely observed in all of our previous studies concerning genetic restrictions of T-B-cell cooperative interactions. Although the basis for differences in the studies reported here when compared to observations made in cytotoxic T-lymphocyte systems is unclear, and could reflect genuine mechanistic requirements concerning what directs H-2 restrictions in helper T cells and cytotoxic T lymphocytes, respectively, it is also possible that we are placing too much faith in our interpretations of data obtained in bone marrow chimera systems than is perhaps justified by the potentially great fragility of such systems.

Animals↗
PubMed1979

Regulation of IgE antibody production by serum molecules. III. Induction of suppressive activity by allogeneic lymphoid cell interactions and suppression of IgE synthesis by the allogeneic effect.

Antibody responses of the IgE class are, like other immunoglobulin classes, regulated by a finely-tuned network of complex cellular and molecular interactions (1). Previous studies conducted in our laboratory (2, 3) have provided new insights into the differences in control mechanisms that result in individuals manifesting either the high (allergic) or low (nonallergic) IgE responder phenotype. These experiments have shown that certain manipulations (i.e. low dose X-irradiation) convert normally low responder mice to high IgE responders, apparently by diminishing a suppressor T-cell mechanism which normally dampens, rather selectively, IgE antibody production in such individuals. Similar findings have been made by Watanabe et al. (4). Recently, we have been studying the types of manipulations that could reverse the high IgE responsive state back to a low one. These studies (2, 3, 5, 6) have demonstrated that the high IgE responses induced in low responder mice can be substantially diminished, and even abolished, by passively transfusing serum or ascetic fluid from donor mice previously inoculated with mycobacterial-containing complete Freund's adjuvant (CFA). Because the suppressive activity of CFA-immune serum or ascitic fluid is so highly selective for IgE antibody production, we have recently termed these serum substances suppressive factors of allergy (SFA) (2, 3). The present study was undertaken to determine whether alternative means, particularly those that avoid administration of CFA, could be devised for the induction of SFA. Herein, we report the effectiveness of allogeneic lymphoid cell interactions in inducing SFA, both in vivo and in vitro, as well as the potent suppressive effects of an in vivo allogeneic effect on irradiation enhanced IgE antibody production in low responder mice.

Animals↗
PubMed1979

Regulation of IgE antibody production by serum molecules. VI: Preliminary biochemical and immunological characterization of serum molecules active in suppressing IgE antibody production.

Molecules present in the serum and ascites fluids of low IgE responder mice previously inoculated with complete Freund's adjuvant have been analyzed in terms of certain biochemical and immunological characteristics. These studies demonstrate that the active molecules, termed "suppressive factors of allergy" (SFA), are (1) nondialyzable, (2) not associated with low-density or high-density lipoproteins, (3) heat stable, (4) precipitable by ammonium sulfate, and (5) approximately 150,000 daltons in molecular size. Studies with immunoadsorbents prepared from various antisera indicate that the suppressive molecules are (1) not immunoglobulin in nature, (2) not reactive with specific anti-H-2 alloantibodies, but (3) reactive with anti-beta 2m antibodies as well as (4) heterologous antisera raised against CFA-immune mouse serum.

Animals↗
PubMed1979

Immunological tolerance to allergenic protein determinants: a therapeutic approach for selective inhibition of IgE antibody production.

Administration of stable conjugates prepared by coupling protein antigens such as ovalbumin or antigen E of ragweed extract to the synthetic random copolymer of D-glutamic acid and D-lysine (D-GL) is effective in inducing a state of long-lasting, antigen-specific immunological tolerance in experimental animals. A striking aspect of the tolerance induced by protein-D-GL conjugates is the remarkable selectivity of the tolerance for antibody responses of the IgE class. Protein-D-GL conjugates of either type were capable of inducing such tolerance both in unsensitized and in previously sensitized animals when administered in appropriate doses. Comparable doses of unconjugated proteins were likewise capable of suppressing IgE antibody production, although the duration of suppression in these cases was significantly less than that observed with protein-D-GL conjugates. If such conjugates act in man as they do in experimental animals, they could be of great value as therapeutic agents in selectively diminishing IgE antibody production while sparing antibody production in the IgG class.

Animals↗
PubMed1979

Biological effects of allogeneic effect factor on T lymphocytes: in vitro induction of cytotoxic T lymphocytes manifesting preferential lytic activity against H-2-identical tumor cells.

The studies reported herein were designed to determine the effects of allogeneic effect factor (AEF), a soluble mediator generated in the course of allogeneic cell interactions, on the differentiation of cytotoxic T lymphocytes in vitro. Normal, unprimed spleen cells from various strains of mice cultured with AEF for 5 days, in the absence of any stimulator cells, developed into cytotoxic lymphocytes capable of lysing target cells in a short-term 51Cr release assay. T lymphocyte-depleted spleen cells did not become cytotoxic when cultured with AEF, and the cytotoxic cells themselves were found to be T lymphocytes. AEF-induced cytotoxic T lymphocytes preferentially lysed H-2-identical target cells. Thus, AEF, as opposed to similar "helper" factors derived from mixed lymphocyte cultures, appears to be unique in its ability to trigger normal, unprimed T lymphocytes to differentiate into cytotoxic T lymphocytes in the absence of specific antigenic stimulation.

Animals↗
PubMed1979

New concepts concerning the clinical control of IgE synthesis.

Prospects for new therapeutic approaches to IgE-mediated allergic diseases have arisen from (1) recent experimental observations that have suggested new concepts concerning the pathogenesis of the allergic phenotype, and (2) adaptation of previously described methods for induction of specific immunological tolerance to problems to allergy. The bases for these new approaches to allergic diseases are summarized herein.

Animals↗
PubMed1979

Adaptive differentiation of murine lymphocytes. III. T and B lymphocytes display reciprocal preference for one another to develop optimal interacting partner cell sets.

Responses to the synthetic terpolymer L-glutanmic acid, L-lysine, L-phenylalanine (GLphi) and hapten derivatives thereof are controlled by two complementing H-2 linked Ir genes in the mouse. F1 hybrids derived from two different nonresponder strains (one of which possesses the alpha and the other beta Ir-GLphi gene) are phenotypic responders to GLphi and 2,4-dinitrophenyl (DNP)-GLphi. Moreover, spleen cells from DNP-GLphi-primed F1 mice can adoptively transfer secondary anti-DNP antibody responses to irradiate been challenged with DNP-GLphi. When, however, GLphi-primed F1 helper T cells are transfered together with the DNP-specific F1 B cells that had been primed in separate mice altogether by DNP coupled to an unrelated protein carrier, such mixtures failed to develop adequate adoptive secondary anti-DNP responses to DNP-GLphi. This contrasted with the ability of the same GLphi-primed F1 T cells to provide helper activity for DNP-primed B cells from responder recombinant B10.A (5R) mice. More important, the apparent defect of GLphi-primed F1 T cells in providing help for DNP-primed F1 B cells (primed to a DNP-protein conjugate) could be readily overcome by using DNP-primed B cells from donor F1 mice primed with DNP-GLphi. As discussed herein, these results suggest that interacting T and B lymphocytes pair off into partner cell sets, any pair of which interact optimally when a "best fit" reciprocal self-recognition occurs between them.

Animals↗
PubMed1979

Regulation of IgE antibody production by serum molecules. IV. Complete Freund's adjuvant induces both enhancing and suppressive activities detectable in the serum of low and high responder mice.

Two biologically active serum molecules manifesting precisely opposite biologic effects, both of which are selective for IgE antibody synthesis, can be detected in the serum and ascites fluids of CFA-immune mice. One activity, described previously, is suppressive and hence termed suppressive factor of allergy (SFA); the other, reported for the first time herein, is enhancing and has been termed enhancing factor of allergy (EFA). The ability to detect one vs the other activity requires certain special manipulations such as different doses of low dose x-irradiation. Conclusive evidence for the existence of two distinct factors mediating these two opposing biologic effects was obtained in studies demonstrating that affinity chromatography on concanavalin A-Sepharose segregated the two molecular entities. Thus, SFA binds poorly or not at all to Con A-Sepharose, whereas EFA binds to Con A and can be recovered in the eluate eluted with the competitive sugar alpha-methyl-D-glucopyranoside.

Animals↗
PubMed1979

Regulation of IgE antibody production by serum molecules. V. Evidence that coincidental sensitization and imbalance in the normal damping mechanism results in "allergic breakthrough".

Experiments presented in this paper were designed to test a new concept concerning the possible pathogenesis of the allergic phenotype. This concept, termed "allergic breakthrough" considers that one of the avenues toward the allergic phenotype involves coincidental sensitization combined with an imbalance in the normal damping mechanism that serves to limit IgE antibody production. The three predictions of this concept that can be tested experimentally are: 1) manipulations that are effective in heightening or re-establishing the damping mechanism should manifest persistence insofar as IgE antibody synthesis to the relevant allergen is concerned; 2) once allergic breakthrough has occurred, the height of production of IgE antibodies specific for the sensitizing agent should remain elevated at levels characteristic of the allergic phenotype, even after the threshold of damping activity has returned to a normal level; and 3) allergic breakthrough should display specificity in that breakthrough would occur in response to subsequent exposure to the specific antigen to which coincidental sensitization initially occurred, but not for other unrelated antigens. The studies presented herein confirm each one of these predictions, thereby providing substantial support for the validity of this concept as one possible distinguishing feature between individuals manifesting the nonallergic and allergic phenotypes, respectively.

Animals↗
PubMed1979

Immunologic tolerance to allergenic protein determinants: properties of tolerance induced in mice treated with conjugates of protein and a synthetic copolymer of D-glutamic acid and D-lysine (D-GL).

Conjugates of proteins and the synthetic copolymer of D-glutamic acid and D-lysine (protein-D-GL) reproducibly induce significant unresponsiveness to the protein antigens in experimental mice. Proteins studied include ovalbumin and antigen E of ragweed extract, the major allergen of ragweed pollen. The unresponsive state 1) can be induced in both unsensitized and previously sensitized experimental animals, 2) is selectively confined to responses of the IgE antibody class, 3) is long lasting, and 4) is highly antigen specific. IgE antibody responses can also be suppressed by administering comparable doses of unconjugated protein alone; however, the unresponsive state induced in this manner is only transient and rebound production of IgE antibody is often observed. Results from the studies of the cellular basis of the protein-D-GL induced unresponsiveness demonstrate that 1) protein-D-GL conjugates do not induce unresponsiveness at the level of protein-specific B cells, 2) tolerance is not induced by virtue of a detectable antigen-specific suppressor T cell mechanism, 3) tolerance is most probably induced in the antigen-specific helper T cell populations. The significant IgE-selective and antigen-specific tolerogenic activity of protein-D-GL conjugates make these compounds potential candidates for use as therapeutic agents in the treatment of IgE-mediated human allergic disorders induced by protein allergens.

Allergens↗