Biomedical subjects

C M Astle

Publications and source records attributed to C M Astle.

4 recordsLinked to original sources

PubMed1979

Processing by the thymus is not required for cells that cure and populate W/WV recipients.

Adult marrow, fetal liver or nu/nu mouse marrow from histocompatible donors was grafted into genetically anemic W/WV recipients, and all three types of grafts cured thymectomized as well as intact W-anemic recipients. With the latter two types of graft, the genetic anemia was cured by cells that could not have been processed in a mature thymus, since the adult recipients were thymectomized before receiving the grafts, the nu/nu donors were congenitally thymusless, and the fetal donors were used at 16 days of gestation. Chromosome-marked marrow grafts were used to show that immune systems were populated to similar degrees in thymectomized and intact W/WV recipients. Therefore, the cells derived from the donor marrow graft that partially populate the immune systems of W-anemic recipients do not require thymus processing. Small numbers of liver rudiment or yolk sac cells from fetal donors less than 12 days old failed to cure W/WV recipients, even when mixed with adult thymus cells. Therefore, the lack of adequately developed thymic helper cells appears not to be the reason why early fetal hemopoietic stem cells fail to cure W/WV recipients.

Aging↗

PubMed1978

Loss of proliferative capacity in immunohemopoietic stem cells caused by serial transplantation rather than aging.

Marrow stem cell lines from old donors and those from young controls gave equally rapid rates of colony growth on spleens of irradiated mice. Old and young stem cell lines competed equally well with chromosomally marked marrow stem cells from a young donor in producing cell types that are stimulated by bleeding; old cells competed 70% as well as young in producing cell types stimulated by phytohemagglutinin (PHA) in vitro. After a single serial transplantation, the rates of colony growth declined 1.5- to 2.5-fold, and the ability to compete declined 2- to 4-fold for bleeding-stimulated and 4- to 10-fold for PHA-stimulated cells. Thus, immediate stem cell proliferative capacities decline much more after one serial transplantation than after a lifetime of normal function.

Animals↗

PubMed1977

Cell lines from old immunodeficient donors give normal responses in young recipients.

Two different immune responses were compared in spleen cells obtained from old and young CBA/HT6J mice. Spleen cells from old mice (23 to 33 months) responded about half as well as did spleen cells from young mice (4 to 10 months) in the adoptive transfer anti-sheep red blood cell (SRBC) plague-forming assay, and caused slightly less than half the uptake of tritiated thymidine in response to phytohemagglutinin (PHA) in vitro. Marrow stem cell from some of the old and young mice whose splenic immune responses were tested were transplanted into irradiated young CBA/CaJ recipients. Seven to 17 weeks later these same immune responses were tested in the spleen cells of these young recipients, and the T6 chromosome marker was used to identify donor cells. Old animals' responses varied greatly, perhaps due to suppressing cells or factors in some individuals. Therefore, cells were never pooled and the responses of receipients were compared to the responses of the donor whose marrow had populated them. The response for a particular old donor, or for the recipients of its stem cells, was divided by the response for the young control used with that donor, or for its stem cell recipients. This was called the old/young ratio. With original donors with an old/young ratio for the SRBC response of (mean +/- S.D.) 0.35 +/- 0.14, The old/young ratio for that same response in the recipients was significantly improved to 1.26 +/- 0.71. In original donors with an old/young ratio for the PHA response of 0.44 +/- 0.17, the old/young ratio in the recipients improved significantly to 0.86 +/- 0.27. Thus, little or none of the decline with age in these immune responses was intrinsic to the old lymphoid stem cells.

Aging↗

PubMed1976

Population of lymphoid tissues in cured W-anemic mice by donor cells.

The percentages of donor cells in lymphoid organs of cured W-anemic mice were determined by using donors with the T6 chromosome marker. W-anemic recipients of two different genotypes were cured by marrow or spleen grafts from histocompatible normal T6/T6 or T6/+ donors. After 2 to 10 months, almost all proliferating cells in the thymuses and marrows, and approximately 75% in the spleens of cured mice were of donor type. However, only 30-40% of the proliferating cells in recipient lymph nodes and 10-20% in their Peyer's patches were of donor type. Percentages of donor cells in marrows and spleens remained high hemopoietic cell division was stopped by injections of erythrocytes. All tissues were slightly less repopulated by donor cells in W-anemic recipients cured by spleen cells compared with those cured by marrow cells. These results were not altered by matching recipients and donors to avoid possible graft versus host reactions, or by removing the thymus of a recipient before it was cured. The fact that the repopulating cells are not all donor type suggests that there are at least two classes of precursor cells that populate the immune system of W-anemic mice, and that not all classes are derived from the grafted cells. Cured W-anemic mice may provide a unique system in which different types of precursor cells of the lymphoid system can be distinguished.

Anemia, Macrocytic↗