The trouble with T cells.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
V J Wallis
Publications and source records attributed to V J Wallis.
Induced type-B reticulum cell neoplasia in mice III. The importance of T-cell proliferation and cellular relocation in accessory cell transformation.
After the transfer of spleen cells from old CBA/T6T6 mice (greater than 75 weeks) into young syngeneic CBA/Ca recipients there usually follows a selective expansion of the donor T-cell population and the emergence of type B reticulum cell neoplasms (RCN-B), also of donor origin though probably derived not from the T-cells but from lymphoid dendritic accessory cells. As few as one million injected cells led to significant donor T-cell hyperplasia and tumour induction. Injection of cells from young donors did not have such consequences. Similar tumours were induced by transferring syngeneic cells in both C57BL and DBA/2 mice, although in the latter strain there was no requirement for the injected cells to derive from old donors. It appeared that T-cell proliferation was independent of donor accessory cells or RCN-B induction, since injection of enriched T-cells led to few tumours, although the T-cell chimaerism was indistinguishable from that in recipients of unseparated spleen cells. Development of tumours, however, seemed to be dependent upon stimulated T-cells. Recipients of spleen cells from old T-cell-deprived mice did not develop tumours; conversely, tumours, mostly of donor origin, were induced in recipients of young syngeneic cells when an extrinsic stimulus to T-cell proliferation was provided by continued allostimulation. The apparent selectivity of tumorigenesis for donor cells has led to the proposal that cellular relocation, as a result of transfer, may be an important predisposing factor in malignant transformation in circumstances of T-cell stimulation provided by antigenic challenge or by transfer of T-cells from old donors.
Age Factors↗
Heterogeneity within the hematopoietic stem cell compartment: evidence for a marrow-seeding stem cell distinct from CFU-s.
Using a chromosome marker within a syngeneic system, we investigated the seeding characteristics of murine hematopoietic stem cells after transplantation to irradiated hosts. The chromosome-marked test cells were allowed to compete with normal marrow cells in repopulating the spleen and marrow of irradiated mice. Although the seeding behavior of normal marrow could be predicted from the number of colony-forming units-spleen (CFU-s) transplanted, the marrow seeding of melphalan-treated marrow was 7-fold greater than expected. Repopulation of marrow by spleen cells was less effective than expected from the CFU-s content, while the reverse was true after repopulation by fetal liver cells. These differences were emphasized after treatment of cell donors with melphalan. The results were due primarily to differences in the lodging properties of the transplanted cells, those seeding in the marrow were less sensitive to melphalan than CFU-s. In some instances marrow-repopulating ability could be separated from peak CFU-s activity on a density gradient, suggesting a marrow-repopulating cell exists that is distinct from CFU-s.
Animals↗
Studies on hyperlymphoid mice.
Injection of syngeneic, but chromosomally distinguishable, lymph node or spleen cells into adult mice resulted in both T- and B-lymphocyte chimaerism. In spleen-injected mice haematopoietic chimaerism was also established. It appeared that the donor T lymphocytes were added to the host recirculating T-cell pool so that a hyperlymphoid state was produced. The percentage of donor T lymphocytes declined very slowly in normal mice, but remained stable in adult-thymectomized animals. There was no evidence of a homeostatic mechanism involving destruction of excess peripheral T lymphocytes or grossly affecting the flow of T lymphocytes from the thymus into the recirculating T-cell pool. A preliminary model of the T-lymphocyte system is proposed.
Animals↗
Studies of hyperthymic mice. I. The influence of multiple thymus grafts on the size of the peripheral T cell pool and immunological performance.
Following the implantation of syngeneic chromosomally marked thymuses under the kidney capsule of normal adult mice, donor T cells were found in the blood and other lymphoid organs. The mice were found to have increased numbers of Thy.1-positive cells in spleen and lymph nodes, increased peripheral blood lymphocyte levels and also augmented immune responses to sheep erythrocytes. The contribution made by an individual graft to the donor T cell pool was independent of the number of thymuses grafted as was the growth of the grafts themselves. The results reaffirm that there is no homeostatic feedback control of thymus growth in adult mice.
Animals↗
Studies of hyperthymic mice. II. The influence of thymus grafts on cell flow through the peripheral T-cell pool.
In normal CBA/H mice implanted under the kidney capsule with eight CBA/H.T6T6 neonatal thymus lobes it was observed that the percentage of marked thymus-graft derived T cells in the periphery, after building up to a peak, showed a biphasic exponential decline. The initial decline was very rapid and appeared to be due to loss of the thymus-graft derived cells from the system. The later decline was slower and was the same as that of an introduced cohort of lymph-node lymphocytes. The second rate of decline was, however, considerably more rapid than that of lymph-node cohort in non thymus-grafted mice. We conclude that in multiply thymus-grafted mice the flow of cells through the T-cell pool is more rapid than in normal mice and that in this sense the thymus can be thought to drive the lymphoid system.
Animals↗
On the sparse seeding of bone marrow and thymus in radiation chimaeras.
The repopulation of the thymus was studied in mice after a potentially lethal dose of irradiation and injection of different numbers of syngeneic but chromosomally distinguishable bone marrow cells. The more bone marrow cells were injected, the earlier was the changeover from dividing host cells to dividing donor cells observed. At both 30 and 60 days after irradiation, the number of donor-derived T cells in the peripheral blood responding to phytohemagglutinin was directly proportional to the number of donor bone marrow cells injected, but the number of host-derived T cells was inversely proportional. Experiments in which mistures of two syngeneic chromosomally distinguishable haematopoietic cell populations were injected after irradiation suggested that relatively small numbers of haematopoietic cells can be responsible for repopulating a single femur. Analysis of the thymus showed that the dividing cell populations within the thymus can also derive from very few precursor cells, possibly as few as one or two.
Animals↗