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Generation of cytotoxic T lymphocytes in vitro. VII. Suppressive effect of irradiated MLC cells on CTL response.

Irradiated cells obtained from MLC at the peak of the CTL response caused profound suppression of generation of CTL when added in small numbers at the initiation of primary MLC prepared with normal spleen cells. The inhibitory activity of the MLC cells was not affected by irradiation (1000 rads) but was abolished by treatment with anti-theta serum and complement. The suppression was immunologically specific. The response of A (H-2a) spleen cells toward C3H (H-2k) alloantigens was suppressed by irradiated MLC cells obtained from MLC prepared with A spleen cells and irradiated C3H-stimulating cells, whereas the response of A spleen cells toward DBA/2 (H-2d) alloantigens was affected relatively little. However, if irradiated C3H X DBA/2 F1 hybrid spleen cells were used to stimulate A spleen cells in MLC, addition of irradiated MLC cells having cytotoxic activity toward C3H antigens abolished the response to both C3H and DBA/2 antigens. The response to DBA/2 antigens was much less affected when a mixture of irradiated C3H and DBA/2 spleen cells was used as stimulating cells. Thus, the presence of MLC cells having cytotoxic activity toward one alloantigen abolished the response to another non-cross reacting antigen only when both antigens were present on the same F1 hybrid-stimulating cells. This suppression of generation of CTL by irradiated MLC cells apparently involves inactivation of alloantigen-bearing stimulating cells as a result of residual cytotoxic activity of the irradiated MLC cells. This mechanism may be active during the decline in CTL activity noted in the normal immune response in vivo and in vitro.

Animals↗

Induction of specific suppressor T cells in vitro.

We describe conditions for generating sheep red blood cell-specific suppressor T cells in Mishell-Dutton cultures. The production of specific suppressor cells is favored by increasing antigen dose in the initial culture but can be produced by transferring more cells when lower doses of antigen are used. Transfer of small numbers of cells cultured with low doses of antigen leads to a specific helper effect. Transfer of large numbers of educated cells leads to nonspecific suppression. Suppression can be effected by the effluent cells from nylon wool columns which do not make detectable PFC. A fraction of these cells become resistant to treatment with anti-T cell sera and complement after culture. The suppressor cells are radiation sensitive and must be able to synthesize protein to suppress. They take 2 to 3 days of education to reach maximum suppressive efficiency and will not suppress cultures if added 2 to 3 days after culture initiation. Their production is favored by the absence of mercaptoethanol, suggesting that the observed suppression is not "too much help". The ability to generate specific suppressor cells in vitro should be of great benefit in determining the factors that regulate their appearance in vivo.

Animals↗

[Remote results of long-term mercazolyl treatment combined with irradiation of the the hypothalamo-hypophyseal region in patients with diffuse toxic goiter].

Prolonged mercazolyl therapy (for from 9 months to 10 years) in combination with X-irradiation of the hypothalamo-hypophysial area (sum total dose of 5000 to 15000 rad) led only in 19 of 54 patients with diffuse toxic goiter to normalization of I131 uptake by the thyroid gland and depression of I131 uptake by the thyroid gland in a test with T3, which could indicate recovery from the disease. Despite a stable euthyroid state in 34 of 54 patients there persisted a hyperthyroid type of the curve of I131 uptake by the thyroid gland, and no depression of I131 uptake by the thyroid gland occurred in a test with T3. Thyrotoxicosis relapses were observed in 15 of 34 of the patients of this group. Development of thyrotoxicosis relapses only in the patients in whom pathological tests persisted pointed to the significance of disturbed interrelations in the hypothalamus-hypophysis-thyroid gland system in the genesis of thyrotoxicosis relapses.

Adult↗

Specific, transient suppression of the immune response by HGG tolerant spleen cells. II. Effector cells and target cells.

In a previous report, it was shown that spleen cells from mice made tolerant to human gamma-globulin (HGG)5 could specifically inhibit the immune response of normal spleen cells after adoptive transfer to lethally irradiated recipients. However, that report also showed that the suppressive activity was only transiently associated with tolerant spleen cell populations. It was concluded from those experiments that while suppressive activity could be demonstrated in tolerant spleen cells under certain conditions, such activity was not obligatory for the maintainance of the tolerant state. The experiments presented here were performed to determine the nature of the effector cell(s) and the target cell(s) involved in this system of suppression of the immune response. Treatment of cells from tolerant animals with anti-thymocyte serum and complement to remove thymus-derived (T) cells completely abrogated suppresive activity. Removal of adherent cells from tolerant spleen cells by passage over glass wool columns resulted in partial loss of the suppression. The inhibitory activity of the suppressor cells was resistant to 900 R irradiation regardless of whether the tolerant spleen cells were irradiated before or after adoptive transfer. The cellular target(s) for the supprssor cells was examined by using lipopolysaccharide (LPS) as an alternative source of helper activity for the response to HGG. LPS, injected at the time of the initial antigenic challenge of mice that had been reconstituted with tolerant and normal spleen cells, prevented the expression of suppression against bone marrow-derived (B) cells. However, when LPS was presented only at the time of secondary antigenic challenge, it was unable to overcome suppression of the immune response of reconstituted recipients. Thus, LPS could produce a state where the B cells were resistant to suppression, but LPS could not rescue the responsiveness of B cells once the cells in the reconstituted recipient had been suppressed. In addition, the immune response to both the hapten dinitrophenol (DNP) and the carrier (HGG) were suppressed when recipients of tolerant and normal spleen cells were challenged with DNP6HGG. This indicates that T helper cells are also a target for suppression. The results presented in this paper are discussed in relation to a possible mechanism of suppression which proposes that suppressive activity represents the induction of tolerance in immunologically competent cells by HCG which is closely associated with the tolerant spleen cells.

Animals↗

[Kilovolt-megavolt irradiation techniques for malignant tumors. Characteristics, indication and limits (author's transl)].

For curative effects of irradiation tumour doses of 5000 to 7000 rd are needed. They can be achieved in depth-therapy with conventional kilo-volt techniques only in carcinoma of the larynx and - via additional gamma rays - in radium-X-ray irradiation of the cervix. For all other indications mega-volt techniques are needed. If properly used, their side-effects are less. The kilo-volt technique for malignant tumors remains for palliative indications. Training will have to be undertaken in centres equipped for all types of therapy.

Cobalt Radioisotopes↗

Effect of X rays on virus production and DNA synthesis in adenovirus-infected cells.

The effect of X rays on the process of type 10 adenovirus infection in HeLa cells was tested. CPE development and virus infections titer were lower in the irradiated cells, while CF titer remained unchanged. The rate of DNA synthesis, as measured by 3H-thymidine incorporation, was higher in the infected cells and radiosensitivity of the process was higher in the infected cells compared with uninfected controls.

Adenoviruses, Human↗