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A clonogenic common myeloid progenitor that gives rise to all myeloid lineages.

Haematopoietic stem cells give rise to progeny that progressively lose self-renewal capacity and become restricted to one lineage. The points at which haematopoietic stem cell-derived progenitors commit to each of the various lineages remain mostly unknown. We have identified a clonogenic common lymphoid progenitor that can differentiate into T, B and natural killer cells but not myeloid cells. Here we report the prospective identification, purification and characterization, using cell-surface markers and flow cytometry, of a complementary clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors. Purified progenitors were used to provide a first-pass expression profile of various haematopoiesis-related genes. We propose that the common lymphoid progenitor and common myeloid progenitor populations reflect the earliest branch points between the lymphoid and myeloid lineages, and that the commitment of common myeloid progenitors to either the megakaryocyte/erythrocyte or the granulocyte/macrophage lineages are mutually exclusive events.

Animals↗

Immunization of hu-PBL-SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries.

Antibodies are usually prepared from recently boosted animals and reflect ongoing immune responses. In humans, this is restrictive as ethical constraints generally prevent antigen-boosting. Therefore the rich memory compartment of human antibody responses remains largely untapped. Severe combined immune deficiency (SCID) mice populated with human cells allow the stimulation of human antibody memory without the usual constraints. Here we show how peripheral blood lymphocytes can be stimulated by antigen to produce large secondary responses after transfer to SCID mice. Specific monoclonal human Fab fragments can then be isolated from the mice by repertoire cloning even when the human donor's last contact with antigen was more than 17 years ago.

Amino Acid Sequence↗

Response of remission lymphocytes to autochthonous leukaemic myeloblasts.

Thymidine incorporation in vitro by remission lymphocytes from a total of 6 patients with acute myeloid leukaemia (AML) was measured following stimulation by autochthonous and allogeneic AML blasts and cell lines. The early peak response to autochthonous blasts in 2 of these patients (48-72 h) is consistent with the concept of a population of lymphocytes pre-immunized to antigens carried by the blasts. Although stimulation in one patient was increased in the presence of more stimulating (S) blasts than responding (R) lymphocytes, positive responses in other tests were obtained at an S : R ratio of 1 : 1-5. When different methods of treatment of the stimulating autochthonous blasts were compared with untreated cells, mitomycin C gave the highest stimulation indices 2 out of 3 tests. Tissue culture medium in which autochthonous blasts had been incubated for 3-5 days failed to stimulate either remission lymphocytes alone, or combined cultures of lymphocytes with autochthonous or allogeneic blasts, suggesting that mitogenic factors released from autochthonous blasts are not responsible for lymphocyte stimulation. Treatment of autochthonous or allogeneic AML blasts with glycine-HC1(pH 3-0) to remove putative "blocking" factors failed to increase the stimulatory capacity of the leukaemic blasts.

Antigens↗

Evaluation of the normal-lymphocyte-transfer test.

The normal-lymphocyte-transfer test has been advocated as a method of assessing the immuno-competence of lymphocytes from patients with breast and large-bowel cancer. Evidence is presented in this paper that the methodology is subject to many uncontrollable errors, that the reaction is the result of multiple factors, and that the size of the reaction is related to the age of the patient and not to the extent of the malignancy.

Adult↗

Enhancing and inhibiting effects of spleen cells from tumour-bearing mice on growth of virus-induced primary sarcoma.

The effects of adoptive transfer of spleen cells from tumour-bearing mice on the growth of Moloney murine sarcoma virus (M-MuSV)-induced primary tumours in BALB/c mice were studied. The effects were in 2 directions, depending on the time of lymphocyte inoculation; when spleen cells from tumuor-bearing mice 12 days after M-MuSV inoculation were inoculated into recipient mice before M-MuSV inoculation, the appearance of tumours was significantly delayed and their incidence was reduced, whereas when these lymphocytes were inoculated after the development of tumours in recipient mice, tumour growth was significantly enhanced. The data indicated that these inhibiting and enhancing effects were mediated mainly by T cells. The mechanisms of the parodoxical effects were investigated.

Animals↗