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Biomedical subjects

S K Singhal

Publications and source records attributed to S K Singhal.

At least 73 records · Page 4Linked to original sources

Cell interaction in B/W mice: a reversible defect at the T-cell level.

The anti-SRBC PFC response of old B/W mice can be restored by adding specifically activated T cells or primed spleen cells in vitro as well as by injecting LPS and SRBC in vivo. Since nonresponsive old B/W bone marrow and thymocytes cooperated in a normal manner upon adoptive transfer, this suggested that the lack of response to SRBC in the intact animal was due to a block in T cell activation and not due to intrinsic defects in lymphoid cells necessary to initiate a response. The block in T cell activation might be mediated by a suppressor cell found in old B/W spleens and it was hypothesized that this suppressor might also lead to a loss of self-tolerance.

Aging↗

Immunosuppressive activity of an extract of Listeria monocytogenes.

The effects of treatment of mice with an aqueous extract of Listeria monocytogenes on lymphoid populations and on immune responsiveness were studied. Thymus weight was decreased to a third of the control, whereas spleen weight was proportionally increased as the number of treatments was increased. The total numbers of cells in the thymus and bone marrow were diminished, whereas the number in the spleen was increased. Serum hemolysin production and plaque-forming cell response to sheep erythrocytes were suppressed in treated mice when the extract was given before administration of antigen. Spleen cells from treated mice failed to mount an antibody response upon transfer to syngeneic gamma-irradiated recipients, suggesting that potential antibody-producing cells were impaired by the treatment.

Adrenalectomy↗

T cell activation and cellular cooperation in autoimmune NZB/NZW F hybrid mice.

Old (6 months) overtly autoimmune female NZB X NZW F1 (B/W) mice were markedly hyporesponsive to sheep erythrocytes (SRBC). The response to SRBC was restored by a) simultaneously injecting lipopolysaccharide (LPS) with SRBC or b) transferring bone marrow and thymocytes with SRBC into lethally x-irradiated (100 R) syngeneic old recipients. The in vitro PFC response of old B/W spleen cells to SRBC was restored by adding in culture a) theta-positive and radioresistant spleen cells from old B/W mice primed with homologous antigen or b) activated T cells from the spleens of lethally x-irradiated (1000 R) old B/W mice injected with old syngeneic thymocytes and SRBC but not horse erythrocytes. Various populations of unprimed lymphoid cells from young (4 to 6 weeks) female B/W mice, which respond normally to SRBC, were not capable of restoring the response of old syngeneic mice in vitro or in vivo. These results suggest the existence of a suppressor of T cell activation and/or B and T cell interaction in old autoimmune B/W mice.

Absorption↗

In vitro induction of specific unresponsiveness of immunologically reactive, normal bone marrow cells.

Normal rabbit bone marrow cells have been studied according to their immunological reactivity in vitro. The test system involved stimulation by antigen after the subsequent stimulation into cellular proliferation by measuring the uptake of tritium-labeled thymidine. Specific separation of immunological reactivity was obtained by filtration of cells through antigen-coated bead columns. All experimental evidence supported the view that this separation was due to the existence of preformed antibody molecules on the outer cell surface of the antigen-recognizing cells. The response to antigenic stimulation was shown to be strictly dose related and, using supraoptimal concentrations of one antigen, no increased DNA synthesis was recorded. That this state of unresponsiveness represented a state of immunological paralysis was indicated by the normal response of these cells to stimulation by a second antigen in optimal concentration. Thus both methods, cell separation on antigen-coated columns or induction of specific unresponsiveness by antigen in vitro, can produce a cell population specifically devoid of cells reactive against a given antigen.

Animals↗

Cells involved in the immune response. IV. The response of normal and immune rabbit bone marrow and lymphoid tissue lymphocytes to antigens in vitro.

Cell suspensions of immune rabbit lymph nodes and spleen were capable of undergoing blastogenesis and mitosis and of incorporating tritiated thymidine when maintained in culture with the specific antigen in vitro. They did not respond to other, non-cross-reacting antigens. The blastogenic response obtained with immune lymph node cells could be correlated with the antibody synthesizing capacity of fragment cultures prepared from the same lymph nodes. Cell suspensions of immune bone marrow responded to non-cross-reacting antigens only whereas cell suspensions of immune thymus, sacculus rotundus, and appendix did not respond when exposed to any of the antigens tested. On the other hand, neither fragments nor cell suspensions prepared from lymph nodes, spleen, and thymus of normal, unimmunized rabbits responded with antibody formation and blastogenesis when exposed to any of the antigens. However, normal bone marrow cells responded with marked blastogenesis and tritiated thymidine uptake. The specificity of this in vitro bone marrow response was demonstrated by the fact that the injection of a protein antigen in vivo resulted in the loss of reactivity by the marrow cell to that particular antigen but not to the other, non-cross-reacting antigens. Furthermore, bone marrow cells of tolerant rabbits failed to respond to the specific antigen in vitro. It was also demonstrated that normal bone marrow cells incubated with antigen are capable of forming antibody which could be detected by the fluorescent antibody technique. This response of the bone marrow cells has been localized to the lymphocyte-rich fraction of the bone marrow. It is concluded that the bone marrow lymphocyte, by virtue of its capacity to react with blastogenesis and mitosis and with antibody formation upon initial exposure to the antigen, a capacity not possessed by lymphocytes of the other lymphoid organs, has a preeminent role in the sequence of cellular events culminating in antibody formation.

Animals↗