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Biomedical subjects

M Feldman

Publications and source records attributed to M Feldman.

At least 541 records · Page 30Linked to original sources
PubMed1972

Thymus-derived lymphocytes: humoral and cellular reactions distinguished by hydrocortisone.

Lymphocytes derived from the thymus (T cells) take part in the induction of humoral antibody and also effect cell-mediated graft-versus-host reactions. Preliminary treatment of mice with hydrocortisone caused an inhibition of T-cell function in humoral immunity, while enhancing the graft-versus-host reactivity of the same population of spleen cells. This suggests that different types of T cells participate in cellular and humoral immune reactions.

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PubMed1972

Fractionation of antigen reactive cells on a cellular immunoadsorbent: factors determining recognition of antigens by T-lymphocytes.

Monolayers of mouse fibroblasts were used as cellular immunoadsorbents to separate rat lymphocytes that recognize specific mouse histocompatibility antigens. Normal lymphocytes were incubated on fibroblasts of strain C3H/eb, and nonadherent cells were separated from adherent cells, then transferred for sensitization onto fresh monolayers of C3H. When tested on (51)Cr-labeled target monolayers the nonadherent cells manifested significantly lower cytotoxicity than the adherent cells. However, the nonadherent cells could be sensitized against mouse fibroblasts of an unrelated H-2 phenotype (strain Balb/c). The immune specificity of the adherence was further demonstrated by a stepwise adsorption, which resulted in complete loss of the capacity to acquire specific lytic activity towards C3H antigens. Lymphocytes recognizing strain-specific antigens of the mouse were separated at 37 degrees (not at 0 degrees or 4 degrees ); separation was inhibited after treatment with dinitrophenol, sodium azide, or trypsin. Prior treatment with neuraminidase rendered the lymphocytes suceptible to separation at 0 degrees .

Adsorption↗
PubMed1971

The development of hypersensitive lymphocytes in cell culture.

An in vitro cell-mediated immune response to pokeweed mitogen (PWM) is described. Rat lymphocytes were stimulated by PWM, by phytohemagglutinin (PHA), and by concanavalin A (ConA). In the presence of PWM only a fraction of the lymphocytes underwent blastogenesis. This was in contrast to the apparent total blastogenesis obtained in response to PHA or ConA. When blast cells derived from each of the mitogens were plated on rat fibroblast monolayer in the absence of mitogen they differentiated into a distinct type of lymphocyte termed "secondary lymphocyte." Addition of mitogens to cultures of these lymphocytes resulted in a retransformation to blast cells. The secondary lymphocytes were tested for their ability to effect lysis in the presence of each of the three mitogens. In. the presence of PWM, lysis of fibroblasts produced by PWM-lymphocytes was considerably more efficient than lysis obtained by ConA- or PHA-lymphocytes. No difference in effect on target fibroblasts was obtained when the three types of secondary lymphocytes were tested in the presence of either PHA or ConA. The stimulating action of PWM on lymphocytes was shown to be immunologically specific. No such specificity was found in the case of PHA or ConA. The results are interpreted to indicate that PWM combines with cell membranes and acts on the lymphocytes as a "transplantation antigen." Lymphocytes capable of responding to "PWM-transplantation antigen" transform to blast cells capable of specifically lysing PWM-conjugated fibroblasts. In the absence of the mitogen, PWM-induced blast cells differentiate to lymphocytes hypersensitive to PWM.

Animals↗
PubMed1971

Rejection of tumor allografts by mouse spleen cells sensitized in vitro.

This paper reports a model system of cellular immunity in which allosensitization of mouse spleen cells is induced in vitro. Allosensitization was achieved by culturing spleen cells upon monolayers of allogeneic fibroblasts. The ability of the spleen cells to inhibit the growth of tumor allografts in vivo served as a functional assay of sensitization. We found that unsensitized spleen cells or spleen cells sensitized against unrelated fibroblast antigens had no inhibitory effect on the growth of allogeneic fibrosarcoma cells when they were injected together into irradiated recipients. In contrast, spleen cells which were specifically allosensitized in vitro were found to be highly effective in inhibiting the growth of an equal number of allogeneic tumor cells. Several times more spleen cells from mice sensitized in vivo were required to produce a similar immune effect. This confirms the findings of previous studies which indicate that sensitization in cell culture can promote the selection of specifically sensitized lymphocytes. Preincubating sensitizing fibroblasts with allo-antisera blocked the allosensitization of spleen cells. This suggests that antibodies binding to fibroblasts may inhibit the induction of sensitization by competing with lymphocytes for antigenic sites. Mouse spleen cells which were able to recognize and reject tumor allografts in vivo were unable to cause lysis of target fibroblasts in vitro. Such fibroblasts, however, were susceptible to lysis by rat lymphoid cells sensitized by a similar in vitro method. These findings indicate that the conditions required for lymphocyte-mediated lysis of target cells may not be directly related to the processes of antigen recognition and allograft rejection in vivo.

Animals↗
PubMed1971

Autosensitization in vitro.

Autosensitization of rat or mouse lymphoid cells against syngeneic fibroblast antigens was induced in cell culture. Rat lymphoid cells autosensitized by this method were able to produce immunospecific lysis of syngeneic target fibroblasts in vitro or GvH reactions in newborn rats. Autosensitized mouse spleen cells mediated similar GvH reactions when injected into newborn mice. The nature of the system used to induce immunity in vitro appears to argue against the possibility that lymphocytes capable of reacting against self-antigens could arise by mutation in cell culture. Hence, it is likely that cells potentially reactive against self-antigens preexisted in the lymphoid cell donors. The ability of autosensitized cells to mediate immune reactions in vivo suggests that the immunogenic self-antigens present on sensitizing fibroblasts also were accessible in the intact animals. Loss of natural self-tolerance in vitro, therefore, can be explained most simply by the existence of lymphocytes which are reversibly tolerant to self. Hence, ontogenic elimination of potentially self-reactive cells may not be the only basis for natural tolerance. Regulatory mechanisms, such as antigen excess, may have to function in vivo to prevent differentiation of self-tolerant lymphocytes. These regulatory mechanisms appear to be annulled in the cell-culture system. The present system thus may offer a new approach to studies of tolerance and regulation of cellular immunity.

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