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D Eidinger

Publications and source records attributed to D Eidinger.

36 records · Page 2Linked to original sources
PubMed1972

Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation.

The primary and secondary immune responses to thymus-dependent and -independent antigens were evaluated in normal male and female mice and in castrated male mice. Both IgM antibody production in the primary response and IgG antibody production in the secondary response were enhanced in females vs. males of equivalent age. Castration of the male converted this animal to a female in terms of responsiveness to the thymus-dependent group of antigens, while inducing equivalent or even greater enhanced responsiveness over the female to the thymus-independent antigen, polyvinylpyrrolidone. Further characteristics of the changes in lymphoid organs were determined in the castrated animal vs. normal males and females. It was shown that the spleen and thymus became markedly hyperplastic, the organ weights exceeding the female, which in turn were greater than in the male. The enhanced weight of the thymus was shown to be due to increased numbers of cortisone-sensitive cells, the absolute number of cortisone-resistant cells remaining equivalent to normal males and females. Thus, the increased thymic weight of the female also resided in the cortisone-sensitive population. Peripheral lymphocyte counts in castrated animals exceeded both normal males and females. Further experiments in gonadectomized males provided evidence that increased thymic cell activity per se played a role in enhanced response to thymus-dependent antigens, but that a thymic-derived hormone mediated the enhanced effect to the thymus-independent antigen in the castrated animal. The capacity for loss of androgenic hormone-producing tissue to generate enhanced differentiation of stem cells was denoted by experiments in which numbers of spleen colonies and uptake of (59)Fe, employed as an index of hematopoiesis 1 wk after reconstitution of lethally irradiated castrated and normal recipients, were enhanced in gonadectomized male animals. Thus, in summary, changes in sex hormone levels exerted a marked influence on immune responsiveness and stem cell differentiation, by increasing numbers of functioning cells, by promoting cellular differentiation, as well as by promoting cellular function via hormonal effects.

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PubMed1972

Classification of thymus-derived and marrow-derived lymphocytes by demonstration of their antigen-binding characteristics.

Antigen-binding cells of T and B origin can readily be determined by quantitating the number of sheep erythrocytes per rosette after glutaraldehyde fixation. The T(1) and T(2) populations have low antigen-binding properties and are very unstable without fixation. The B(1) and B(2) populations are stable and correlate with precursor and secretory cells. Fixation of rosettes permits a sensitive test for studying differentiation of T and B cells.

Animals↗
PubMed1971

Further studies of antigenic competition. 3. A model to account for the phenomenon based on a deficiency of cell-to-cell interaction in immune lymphoid cell populations.

A striking correlation between the capacity of an antigen to nonspecifically suppress humoral immune responses of subsequently administered antigens which are non-cross-reacting, i.e. to manifest antigenic competition and produce enlargement of spleen size through cell proliferation, was found. Increase in spleen size was always accompanied by a drop in the normal proportion of thymus-derived cells to non-thymus-derived cells. Various means of altering the immune response to the initial antigen, and hence, the capacity of that antigen to suppress in a model of antigenic competition were performed and correlated with changes in spleen size and in the proportion of theta-positive cells in the spleen. In all instances, when the experimental condition reduced or abolished antigenic competition, the increase in spleen size and reduction in the proportion of theta-positive cells in the spleen was reduced or abolished. Furthermore, under conditions in which the suppressive capacity of the initial antigen was unaltered, the increase in spleen size and reduction in theta-proportion occurred normally. Finally, the better the suppression in a model of antigenic competition, the greater the increase in spleen size and reduction in the proportion of theta-positive cells. On the basis of these observations, it appears that there is a relationship between spleen enlargement through clonally restricted cell proliferation and the expression of antigenic competition; one cannot have the latter without the former. It is postulated that the immunological lesion associated with antigenic competition resides at the level of interference with cell interaction between thymus-derived antigen-reactive cells and marrow-derived antibody-forming cells. This occurs as a result of a relative "diluting out" of cells of both populations carrying antigenic specificity differing from the one(s) which induced the dilution effect in the first place. The net effect of this is to decrease the chance of a "hit" or interaction between a marrow-derived and thymus-derived cell of the same specificities. This mechanism, which is compatible with theories of clonal selection, and which in fact is dependent upon them, supports the view that the term "antigenic competition" is a misnomer; there is no competition by the antigens for anything. The term "antigen-induced suppression" is suggested as a more suitable alternative.

Animals↗
PubMed1971

A cellular deficit in the reconstitutive capacity of immune populations of lymphoid cells demonstrable in studies of delayed hypersensitivity in mice. Evidence for thymus-bone marrow cell synergism.

A cell-transfer system was employed in the present work to investigate several characteristics of the capacity of immune and normal lymphoid cells to transfer the delayed response to methylated human serum albumin in lethally irradiated syngeneic recipients. Spleen cells derived from donor mice immunized with goose erythrocytes were far less effective in transferring responsiveness when compared with equal numbers of normal cells. Statistical analyses indicated a frequency of 1 reactive cell or cell unit in 1.3 x 10(7) normal cells and in 6.2 x 10(7) immune cells. These findings provided confirmatory evidence that antigen-induced suppression (antigenic competition) employing sequential administration of two non-cross-reacting antigens is due to relative deficits of immunocompetent cells generated by lymphoproliferation in lymphoid tissues secondary to immunization with the initial antigen. The cellular deficit in the immune population was shown to be resident in a thymus cell population, which restored the number of responders to a level equivalent to the normal population. The thymic cell was akin to the antigen-reactive cell. The cell limiting the degree of response, that is the effector cell for both normal and immune cell populations, was of bone marrow origin. Both populations of cells were shown to act in synergy to reconstitute the delayed response to the antigen.

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PubMed1968

The effect of antigenic competition on various manifestations of humoral antibody formation and cellular immunity.

The effect of antigenic competition on various parameters of humoral antibody formation and cellular immunity was studied in mice. Several pairs of antigens were employed in the investigation of the competitive aspects of induction of humoral antibody formation. Induction of a primary immune response to hemocyanin in Swiss white female mice moderately suppressed the induction of both 19S and 7S antibody formation to goose or rat erythrocytes. Suppression of 7S antibody formation was maximal when a time interval of 1-3 days separated the sequence of injections, although suppression was noted for intervals of up to 14 days. The induction of a primary immune response to rat RBC, the second of the two antigens in sequence, also suppressed The induction of both 19S and 7S antibody formation to goose RBC when appropriate intervals of 1-3 days were employed between injections. The induction of a secondary immune response to rat RBC totally suppressed the primary induction of both 19S and 7S antibody formation to goose RBC administered in the appropriate time sequence. Subsequently, it was shown that the secondary immune response to the suppressed antigen (goose RBC) elicited 30 days after induction of a primary immune response (5 days after secondary immunization with rat RBC) was characterized by deficient 19S and 7S antibody production. These levels were suppressed even in comparison with a normal primary immune response to this antigen. The results were interpreted in part on the basis of a deficiency of formation of primed cells associated with immunological memory. Alternatively, evidence was obtained for the development of a split type of immunological tolerance in 6 of 10 animals studied, since a total suppression of 7S antibody production was obtained in association with deficient 19S antibody synthesis (titers < 1/10). The induction of a primary immune response to several antigens in A/J female mice suppressed the processes of cellular immunity as manifested by prolonged survival of skin grafts from C57 BL/6J female donors. These results were interpreted as evidence for the existence and utilization of processing cells by the initial immune stimulus yielding a deficiency of cells available for processing the second antigen administered in sequence.

Animals↗
PubMed1967

The immune response to sheep erythrocytes in the mouse. I. A study of the immunological events utilizing the plaque technique.

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level. The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1-2 days and 2-3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2-3 days. The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr. The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus. Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy. The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody. Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.

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