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Biomedical subjects

D B Wilson

Publications and source records attributed to D B Wilson.

At least 379 records · Page 21Linked to original sources
PubMed1970

Mixed lymphocyte reactions and tissue transplantation tolerance.

The induction of tolerance of Lewis histocompatibility antigens in BN rats inoculated at birth with BNI Lewis F(1) hybrid bone marrow cells, as revealed by the prolonged survival of Lewis skin grafts, is accompanied by markedly decreased reactivity in the mixed lymphocyte interaction. Blood lymphocytes from animals inoculated with lymph node cell suspensions also display diminished proliferative reactivity to hybrid BN/Lewis cells in the interaction. However, these recipients are not tolerant of Lewis skin grafts. Blood lymphocytes from BN rats inoculated neonatally with Lewis thymocytes fail to display any level of unresponsiveness in vitro, and such animals are not tolerant of Lewis skin grafts. The results suggest that in rats skin and marrow cells have histocompatibility antigens that are absent or poorly expressed on lymph node cells and thymocytes.

Animals↗
PubMed1970

Protein chain initiation in rabbit reticulocytes.

About 15% of the nascent alpha-chains isolated from in vivo labeled rabbit reticulocytes have methionine as their amino terminal amino acid. The methionine is predominantly on the shortest nascent chains, suggesting that methionine initiates the synthesis of rabbit hemoglobin and is rapidly removed during further synthesis.

Amino Acid Sequence↗
PubMed1970

Quantitative studies on the mixed lymphocyte interaction in rats. IV. Immunologic potentiality of the responding cells.

Studies were designed to provide some explanation for the unexpectedly large proportion (2%) of parental rat strain peripheral blood lymphocytes that are reactive in the mixed lymphocyte interaction (MLI) to a strong homologous transplantation isoantigen(s) present on cells from an F(1) donor. The possibilities considered involve nonspecific activation and multispecific reactivity on the part of the responding cells. The essential findings of this study were: (a) In 3-way mixed cultures, lymphocytes obtained from tolerant animals were not "recruited" to proliferate in the presence of cells from normal, isologous donors which were in the process of responding to F(1) cells bearing the tolerance-inducing antigens. With the use of chromosome markers and normal and tolerant parental strain donors of different sexes, the responsive cells were identified and proved to be derived from the normal and not the tolerant donor. (b) The magnitude of the proliferative response is increased additively when potentially reactive cells are exposed to two antigen systems simultaneously. On the other hand, doubling the "gene-dosage" of the genetic determinants of the H isoantigens employed had no effect on the responding cells. (c) A state of induced immunologic tolerance to one H isoantigen system did not alter the response capacity of cells from such a donor to an alternative antigen system. (d) Mixed cultures of heterologous cells from human and rat donors displayed a proliferative response which was less than that of homologous mixed cultures from human or rat donors. Prior sensitization of rat donors with human cells, however, greatly increased the mitotic activity of rat lymphocytes stimulated with human cells. These results suggest that the large number of responsive cells in the MLI do not include a significant number recruited or activated in some nonspecific manner. Rather, they appear to be fully specific in their response capacities so that a given lymphocyte does not react to a multiplicity of different antigens. The degree of proliferation depends on the number of different antigen systems presented to the responding population and not on the number of genetic determinants or "gene dosage" of a given isoantigen system. Finally, on a cell-for-cell basis, the peripheral blood lymphocyte population contains more cells reactive to histocompatibility isoantigens within the species than to heterologous antigens of a different species.

Animals↗
PubMed1968

Quantitative studies on the mixed lymphocyte interaction in rats. 3. Kinetics of the response.

The proliferative interaction of cultured rat lymphocytes of immunogenetically disparate origin-the mixed lymphocyte interaction-was employed as an experimental model to examine the initial stages of the immune response mechanism. Using mixed cultures of cells derived from parental strain and F(1) hybrid rats, in which only the parental lymphocytes respond, the following observations were made on the magnitude and kinetics of the reaction. After initiation of the cultures, there was a latent period of approximately 40 hours during which time no mitotic activity was detected. This inactive phase was followed by a period of proliferation in which previously nondividing cells entered the mitotic cycle for the first time. Activity in the cultures, as detected by incorporation of radioactive thymidine and measured by radioautography or scintillation spectrometry, increased exponentially with a doubling time (T2) of 9-10 hr. In this exponential proliferative phase, lasting approximately 100 hr, the dividing cells underwent a series of rapid sequential divisions with a generation time (Tc) of 8 hr, and few, if any, dropped out of the mitotic cycle. In addition to the cells which first entered mitosis at the beginning of the proliferative phase and then proceeded through multiple divisions, significant numbers of new, previously nondividing cells continued to enter the mitotic cycle during the entire exponential growth phase. The total number of these newly responsive, first division cells throughout the total culture period amounted to 1-3% of the original parental cell inoculum. This is a surprisingly large proportion of peripheral blood lymphocytes with demonstrable reactivity to a particular antigen system, if it is assumed that these first division cells in vitro are functionally related to the hypothetical antigen-sensitive cells which proliferate and differentiate into immunological effector cells. At present there is no entirely satisfactory explanation for this large number of reactive cells in the mixed lymphocyte interaction.

Animals↗
PubMed1967

Quantitative studies on the mixed lymphocyte interaction in rats. I. Conditions and parameters of response.

Some of the conditions and parameters of the proliferative response in the mixed lymphocyte interaction have been studied with the use of culture inocula consisting of lymphoid cells from various immunogenetically diverse, isogenic strains of rats. Procedures are described by which consistent culture responses can be obtained which are measurable in terms of incorporation of radioactive thymidine into a trichloroacetic acid precipitable cell fraction. Results of experiments with this "mixed lymphocyte interaction" show that (a) Incorporation of thymidine into the mixed cultures is detectable only during and after the 4th day of incubation. Use of culture inocula derived from the thoracic duct or partially purified suspensions of lymphocytes from the peripheral blood provides further evidence that it is the small lymphocyte which synthesizes DNA in these cultures. The addition of peritoneal exudate cells, presumably containing some macrophages, to the mixed lymphocyte cultures does not alter the kinetics of the response. (b) Proliferative responses occur in mixed cultures of cells only when the donors differ by alleles at the important Ag-B histocompatibility locus. (c) Proliferative reactivity in mixed cultures of lymphocytes from parental and hybrid donors is unidirectional. With the use of chromosomally marked cells from donors of different sexes, it was established that only parental lymphocytes are dividing in mixed cultures of parental and hybrid cells. The results of these experiments strongly support the premise that the proliferative response in mixed cultures of lymphocytes represents a de novo immunologic reaction on the cellular level against histocompatibility antigens.

Animals↗
PubMed1967

Quantitative studies on the mixed lymphocyte interaction in rats. II. Relationship of the proliferative response to the immunologic status of the donors.

The influence of the immunologic status of the cell donors on the proliferative behavior of rat lymphocytes in the mixed lymphocyte interaction has been studied. Mixed cultures of cells from various parental and F(1) combinations having morphologically distinguishable sex chromosomes exhibited unidirectional proliferative reactivity. The mitotic figures were predominately of parental origin. Lymphocytes from donors made tolerant at birth to homologous transplantation isoantigens were specifically unreactive against cells bearing antigens of the tolerance inducing strain, but not to indifferent third party homologous lymphocytes. Cells from animals that had been surgically thymectomized at birth exhibited a markedly and sometimes totally diminished reactivity against homologous lymphocytes. Presensitization of the cell donors resulted in a curtailment of proliferative reactivity in cultures with cells bearing the immunizing antigens. This may reflect the destructive properties that lymphocytes from sensitized animals are known to possess. The results of these experiments show that the proliferative activity of lymphocytes in the mixed lymphocyte interaction accurately reflects the immunologic status of the cell donors, and these findings provide further support for the premise that the mixed lymphocyte interaction represents a primary immunologic response by cells in culture against homologous cells bearing histocompatibility antigens.

Animals↗