Blast Transformation Reaction Research Articles

Metabolic immunodepression and metabolic immunotherapy: an attempt of improvement in immunologic response in breast cancer patients by correction of metabolic disturbances.

The effects of administration of phenformin and clofibrate to 32 breast cancer patients who underwent radical mastectomy and suffered from hormonal metabolic disturbances involving a decline in immunologic response were investigated. It was demonstrated that treatment with these drugs during 2--7 months results in an improvement in metabolic parameters and delayed hypersensitivity reaction to DNCB, tuberculin and candidin (75.5% of cases), an increase in T lymphocyte count (56.3%) and an improvement of the reaction of lymphocyte blast transformation (66.6%). The improvement in the immunologic status of the patients persisted for 6--8 weeks after the stoppage of phenformin administration; a gradual decline in immunologic response and return to the original level were recorded 4--6 months after stoppage and phenformin therapy. The effect of clofibrate on metabolic and immunologic parameters did not manifest itself as soon as 6--8 weeks after stoppage. Elimination of metabolic immunodepression, which gradually develops in the course of normal ageing and tumor process, should be the main objective of metabolic immunotherapy. To this end, therapeutic means, other than phenformin and clofibrate, may be used provided they exert the same effects on carbohydrate-fat metabolism. The desirability of study of the effects of a long-term course of drugs of this kind on the therapy of cancer patients is discussed.

Inhibition of in Vitro Nickel Sulfate Reaction by Anti-HLA-D/DR Antisera. Lack of Demonstrable Suppressor Cells in Peripheral Blood in Nickel Unresponsiveness in Man

A nickel sulfate induced lymphocyte blast transformation reaction in vitro was specifically inhibited by anti-HLA-D/DR antisera, which indicates the requirement of HLA-D/DR antigens in cellular cooperation. Macrophages are effective antigen presenting cells in the in vitro nickel reaction and this step could be the site of an HLA-antigen function in the recognition of "self." It was shown that macrophages of an HLA identical, healthy sibling could offer proper "help" to macrophage-depleted lymphocytes of the nickel allergic subject in evoking a nickel reaction. Thus, in this respect, the function of macrophages in nickel allergy is not different from that in a nickel-unresponsive state. The nickel unresponsiveness in healthy subjects is probably not due to specific suppressor cells because HLA identical lymphocytes from the healthy siblings could not suppress the nickel induced blast transformation of the nickel allergic siblings. This suggests that a deletion of sensitized clones in the periphery is the more probable mechanism of unresponsiveness in healthy subjects.

Immunologic activity of human lymph cells in the blast transformation reaction

The effect of the synthetic inhibitor-antioxidant belonging to the 3-hydroxypyridine series (compound OP-6) on the functions of immunocompetent and stem cells of mice was studied. Use was made of the models of synthesis of antibodies to sheep red blood cells (local hemolysis and hemagglutination), of endogeneic and exogeneic colony-formation in (CBA X C57BL)F1 mice as well as skin homotransplantation to CBA mice from C57BL/6 donors. Compound OP-6 was shown to exert an immunodepressant effect on both the humoral and cell immunity, not to decrease the colony-forming capacity of the stem cells and to protect them from irradiation.

Abolition of allogeneic inhibition and changes in differentiation of mouse bone marrow colony-forming cells by syngeneic lymphocytes

A mixture of bone marrow cells and lymph gland lymphocytes of C57BL mice was injected intravenously into F1 (A×C57BL) mice irradiated in a dose of 850 R. Under the influence of syngeneic lymphocytes of the C57BL mice colony-forming cells (CFUs) of the bone marrow proliferated in the F1 mouse hybrids as if they had been in a syngeneic organism. Besides restoration of the number of CFUs capable of forming colonies in a genetically foreign organism, under the influence of lymphocytes the colonies changed their direction of differentiation, with an increase in the number of granulocyte colonies. This process was accompanied by the development of a blast transformation reaction and by hyperplasia of the lymphoid tissue of the recipients' spleens.

Investigation of the blast transformation reaction of lymphocytes in guinea pigs with experimental allergic encephalomyelitis

Experimental allergic encephalomyelitis (EAE) was induced in guinea pigs by injection of myelin from homologous brain in Freund's complete adjuvant. In the incubation period of EAE some animals showed a marked increase in the spontaneous proliferative activity of the blood lymphocytes, assessed in cultures using thymidine-H3. With the development of clinical manifestations of the disease, the spontaneous activity of the lymphocytes reached a maximum and was exhibited in the overwhelming majority of animals. When the clinical picture of EAE was well marked, the response of the lymphocytes to stimulation by myelin preparations was observed mainly if the spontaneous mitotic activity of the cells was low or only moderately increased. Specific antigenic stimulation in vivo connected with the immunopathological process could be the cause of the increasing spontaneous activity of the lymphocytes. The state of nonspecific reactivity of the lymphocytes to phytohemagglutinin in EAE was indistinguishable from that in the control animals.

Human thyroglobulin and thyroid extract as specific stimulators of sensitized lymphocytes.

ABSTRACT Lymphocytes from peripheral blood of patients with various thyroid diseases and of healthy volunteers were tested for blast transformation reaction by human thyroglobulin, thyroid extract, adrenal extract, phytohemagglutinin (PHA) and staphylococcal nitrate (SF). The subjects comprised 9 patients with Hashimoto's disease, 12 hypothyroids, 8 with nontoxic goiter, 10 thyrotoxics, and 15 healthy controls. Lymphocytes from 6 of the patients with Hashimoto's disease were specifically stimulated to transform by human thyroglobulin or thyroid extract, while, among the other groups tested, only one patient with nontoxic goiter demonstrated a significant specific stimulation. It is suggested that the specific blast transformation may be caused by auto-immunization to thyroid antigens.