Biomedical subjects

M J Doenhoff

Publications and source records attributed to M J Doenhoff.

At least 127 records · Page 7Linked to original sources

PubMed1978

The immunodepressive effect of Friend virus. IV. Effects on spleen B lymphocytes.

Splenic immune responses having varying dependence on accessory cell co-operation have been studied after infection of mice with Friend virus. Infection has no effect on cell proliferation or antibody production in cultures stimulated with E. coli lipopolysaccharide. The response in vivo to type III pneumococcal polysaccharide is depressed only moderately. The response to sheep red blood cells is depressed severely both in vivo and in vitro. Depression in vitro is greatly reduced by co-stimulation with E. coli lipopolysaccharide. Depletion of potential suppressor lymphocyte populations by irradiation or adult thymectomy does not ameliorate depression of responses to sheep red blood cells or pneumococcal polysaccharide. Responses after adult thymectomy plus irradiation are not affected by the virus. Although it is known that macrophage and helper T-lymphocyte co-operation are not themselves impaired by infection, these results suggest that there is a direct relationship between severity of immune depression and dependence on co-operation. Implications for the action of the virus are discussed.

Animals↗

PubMed1977

Effects of irradiation, anti-thymocyte serum and corticosteroids on PHA and LPS responsive cells of the mouse.

Peripheral lymphocytes responsive to stimulation by phytohaemagglutinin (PHA) and bacterial lipopolysaccharide (LPS) in culture have been quantitated following treatment of mice with anti-thymocyte serum (ATS), total body irradiation or corticosteroids. The ATS reduced the number of PHA-responsive cells in both blood and spleen, and induced splenomegaly, but it had little deleterious effect on spleen-borne LPS-responsive cells. In contrast, the spleens of mice treated with hydrocortisone acetate were atrophied and the remaining cells had a reduced LPS response and an enhanced PHA response. Total body irradiation impaired both PHA and LPS responsiveness in the spleen. Recovery of PHA responsiveness after either irradiation or ATS treatment was prolonged and was dependent on the presence of an intact thymus; recovery of LPS responsiveness after corticosteroid treatment was more rapid and was thymus-independent.

Animals↗

PubMed1977

The immunodepressive effect of Friend virus III. Effects on spleen T cells.

We have examined various T lymphocyte functions in the spleens of mice infected 4 days previously with Friend viurs (FV) in order to analyse its effect on the antibody response. We have found (a) that infection does not reduce the percentage of T lymphocytes in the spleen, nor their ability to respond to PHA, (b) that infected spleen cells mediate allogeneic augmentation of the primary response to SRBC in vitro, even though their own depressed response cannot be restored via the allogeneic effect, and (c) that infected spleen cells restore responses to SRBC by both allogeneic and syngeneic spleen cell cultures depleted of T lymphocytes. These results suggest that FV does not affect spleen T lymphocyte proliferation of helper function. Since macrophages from infected spleens cooperate normally in the response to SRBC in vitro, we conclude that the immune defect resides in the B lymphocytes.

Animals↗

PubMed1976

The capacity of mitogen-responsive T cells to "home" to their tissue of origin, analyzed by means of chromosome markers.

Lance and Taub (1) showed that when radioactively labeled lymphocytes were injected into a syngeneic mouse and the lymph node cells of this animal transferred to a second syngeneic recipient, the proportion of radioactivity found in the lymph node relative to the amount present in the spleen of the secondary recipient had increased markedly. The interpretation of this result was that some lymphocytes have the capacity to "home" to their organ of origin. The purpose of the experiments described here was to test the "homing" copacity of T cells by a method that did not involve radioactive labeling. It has been shown elsewhere that some or all mouse T cells are stimulated to divide in culture by the mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) (2). We therefore elected to inject karyotypically distinct lymphocytes into syngeneic recipients and to follow their subsequent distribution by culture of lymph node and spleen cells of the recipient with PHA or Con A. In this manner the homing capacities of spleen and lymph node T cells could be determined, and furthermore, the effects of labeling with chromium-51 ((51)Cr) could be assayed with respect to the persistence of mitogen responsiveness in the injected cells.

Animals↗

PubMed1976

Enumeration of polyclonal mitogen-responsive cells in different lymphoid tissues of the mouse.

The relative number of cells capable of responding to Con A, PHA and LPS in the spleen, blood, lymph node and Peyer's patches of CBA mice has been quantified by means of a cytological analysis technique. No difference has been found between Con A- and PHA-responsive cells in spleen and lymph node. The lymphoid tissues of T cell-deprived mice have a reduced content of PHA responsive cells, but LPS responsiveness is within normal limits. Pretreatment of peripheral lymphocyte populations with high concentrations of anti-O antiserum and complement abolishes the response of the treated cells to PHA, but not to LPS, whereas similar treatment with a cytotoxic anti-immunoglobulin serum, which has no effect on PHA-responsive cells, only partially reduces the response to LPS. The results for mitogen responsiveness are discussed with reference to other methods of quantifying T and B cells using cell-surface markers.

Animals↗

PubMed1976

The mitotic activity of, and antibody production by, sensitized lymphocytes quantified after transfer into irradiated recipients.

Adult thymectomized, irradiated CBA mice were reconstituted with bone marrow and thymus grafts derived from congenic strains differing in immunoglobulin allotype. After challenge with heterologous erythrocytes the allotype of the antibody secreted by the chimaeric spleen cells was the same as that of the bone marrow donor. When mixtures of immune and non-immune cells from the two congenic strains were transferred to irradiated recipients, a preponderance of the immune-donor cells was found dividing in the recipients' spleen 3 days after challenge with the immunizing antigen, and the allotype of the antibody-producing cells 7 days after challenge was almost entirely of immune-donor derivation. Further quantitative studies on the number of mitotically reactive cells observed after immunization with heterologous erythrocytes indicate that after primary and secondary challenge the mitotic activity of these cells is increased respectively four and eight times relative to that found in unsensitized cells.

Animals↗

PubMed1975