The kinetics of inhibition with methotrexate and vinblastine of the primary immune response to sheep red blood cells in mice.

Forty-eight or 72 h after immunization with sheep red blood cells, CBA mice were injected intraperitoneally with a single dose of methotrexate or vinblastine, 2.5 mg/kg and 1.5 mg/kg respectively, and then the number of direct plaque-forming cells in their spleen was estimated at 4-h intervals. The PFC growth curve showed an exponential and staircase pattern. After administration of both cytostatics, the PFC numbers in the spleen of mice changed in a wave-like fashion: the increase was accompanied by a decrease. In some parts of the curves obtained the PFC numbers increased or decreased 2 to 7 times within 4 hours. A marked increase in PFC numbers in the controls and in animals treated with both cytostatics occurred at 60, 72--76, 84--88 h of the immune response. It is suggested that methotrexate and vinblastine do not prevent recruitment of precursor cells into PFC and consequently the number of PFC increases. The decrease in PFC numbers under the influence of both cytostatics presumably results from "unbalanced growth".

[Effect of methotrexate on the level of T- and B-lymphocytes]. / Issledovanie vliianiia metotreksata na urovne T- i B-limfotsitov.

Through an analysis of the immune response of mice to sheep's erythrocytes within a system of syngenic transfer the action of Methotrexate on the T- and B-lymphocytes was studied. Splenic cells of donors receiving methotrexate were introduced to lethally irradiated recipients together with the bone morrow or thymus cells. In the recipients' spleen the content of antibody-forming cells and hemolytic foci were determined. It was shown that in recipients receiving splenic cells alone the number of antibody-forming cells and of the foci sharply declined under the effect of methotrexate. Introduction of the bone marrow cells contributed to reconstitution of the response in recipients at the level of the antibody-forming cells, but not at that of the hemolytic foci. At the same time, thymocytes increased the content of the antibody-forming cells up to a level exceeding the control one, as well as the number of foci. The results proof methotrexate capable of inhibiting the proliferation of the T- and B-cells in the spleen of mice, induced by the antigen.

[Immunosuppressive properties of vinblastine and colchicine]. / Izuchenie immunodepressivnykh svoistv vinblastina i kolkhitsina.

The action of vinblastine and colchicine on the populations of antibody-forming cells, their precursors and stem cells using a model of primary immune response and in the transplantation system was studied using techniques by Jerne and Nordin (1963), Kennedy et al. (1965), and Till and McCulloch (1961). It was discovered that vinblastine and colchicine, at single administration 48 hours after immunization, inhibited immune response completely. The administration of colchicine and vinblastine to a donor gave an exponential decrease of in foci-forming cell number in a recipient in the system of syngenic transfer. But at the same time, vinblastine at small doses stimulated population of antibody-forming and stem cells, whereas at large doses it was not effective. Colchicine, in contrast, strongly inhibited both antibody-forming and haemopoietic cells in the recipient.

[Comparative study of antineoplastic and immunosuppressive properties of ftorafur]. / Sravnitel'noe izuchenie protivoopukholevykh i immunodepressivnykh svoistv tsitostatika ftorafura.

In experiments staged on mice with transplantable leukemia L 1210 an immunodepressive and antineoplasic action of phthorafur was studied. Depending upon its dose phthorafur lowered the number of lymphoma colonies and antibody-forming cells in the spleen of the animals immunized with sheep erythrocytes. The maximal immunodepressive action was found to set in following administration of the agent in a dose of 500 mg/kg 24 and 48 hours after antigenic stimulation.

The effect of Trichinella spiralis on graft-versus-host reaction, transplantation immunity and antibody formation.

The effect of Trichinella spiralis in different phases of infection on transplantation immunity, the ability of lymphocytes to induce graft-versus-host reaction, on antibody and plaque-forming cell production was studied. In certain phases of Trichinella spiralis beginhing from the first days of infection and during 40 days significant suppression of transplantation immunity was observed. Thus, on the 24th day of infection skin allograft necrosis occurred much later (26.2 days) as compared with non-infected mice (12.5 days). The spleen cells of C57BL/6j mice infected with Trichinella spiralis on the 22, 29, 36, 42, 56, 72 days either induced slight graft-versus-host reaction in (CBA X C57B1/6j) F1 hybrid mice or did not induce it at all (42nd day of infection). The amount of antibody forming cells in Trichinella-infected mice significantly decreased on the 20, 25, 47, 55th days of infection. Hemagglutinin production to sheep red blood cells was significantly inhibited on the 25th day of Trichinella spiralis infection. The concept of immunodepressors being released from helminths is briefly discussed.

[Kinetic peculiarities of the immunodepressive effect of methotrexate]. / Kineticheskie osobennosti immunodepressivnogo deistviia metotreksata

The content of direct plaque-forming cells (PFC) in the spleen of sheep erythrocytes immunized mice after a single administration to them of 2.5 mg/kg methotrexate on the 48th or 72nd hour of the immune response was measured. The PFC count was determined every 4 hours for 68 hours after introduction of methotrexate. In either of the cases the curve reflecting changes of the PFC count in the spleen was of an undulating nature. The alternating rises and falls of the PFC number proceeded at a high speed, viz. the time of doubling and half-periods of drop-off on individual lengths of the obtained curves was of the order of 2--4 hours. It is suggested that the PFC population accretion is ensured by a synchronous recruitment from the cells-precursors, antigen activated upon introduction of methotrexate. The decline in the number of PFC is, apparently, dependent upon their destruction due to an "unbalanced growth".

[Synthesis of messenger-like RNA in plasma cels producing different clases of immunoglobulins]. / Sintez informatsionnopodobnkh RNK v plazmaticheskikh kletkakh, produtsiruiushchikh razlichnye klassy immunoglobulinov

Electrophoretic analysis of the nuclear poly A RNA cells of the MOPC 21, MOPC 406 and MOPC 41 plasmocytomas demonstrated a similarity in their distribution by the mol wt. Kinetics of the label accumulation in the nuclear poly A RNA of different plasma cells was unitypical. Individual peculiarities of the distribution of the cytoplasmic poly A RNA were expressed for each individual line of the myeloma cells. The majority of the molecules of the heterogenous RNA in the plasma cells were subjected to posttranscription polyadenylation.

[RNA biosynthesis in the microsomes of splenic cells during the inductive phase of the immunological response]. / Biosintez RNK v mikrosomakh kletok selezenki vo vremia induktivnoi fazy immunologicheskogo otveta

RNA labeled with 3H-uridine was extracted from the microsomes of the spleen of the intact and antigen-stimulated mice. A study was made of the composition of this RNA by electrophoresis in polyacrylamide gel. Apart from rRNA, there were revealed in the microsome composition up to 10 RNA components in the mol wt range of from 0.4-10(5) to 7-10(5) dalton and 2 componnents - between 7-10(5) and 1.7-10(6) dalton. Incorporation of 3H-uridine into the rRNA was the maximal 24 hours after the administration of the antigen, whereas the RNA with the mol wt between 0.4-10(5) dalton remaining practically unchanged for a period of three days after the immunization. 3H-uridine incorporation into these RNA was resistant to the action of low antibiotic (actinomycin D) doses. Immunization was not accompanied by the appearance of new, by molecular weight, RNA components.

[Effect of Trichinella spiralis infection on the development of Rauscher leukemia]. / Vliianie invazii Trichinella spiralis na razvitie leikoza Raushera

The influence of Trichinella spiralis on the course of Rausher leukemia in mice was studied. Inoculation of mice with Trichinella spiralis larvae 15, 16 and 30 days before infection with Rausher leukemia virus was shown to stimulate splenomegaly, whereas preinoculation of Rausher leukemia virus at 6, 12 and 18 days before infection with Trichinella spiralis resulted in inhibition of splenomegaly. Under the experimental conditions used, no effect of T. spiralis on reproduction of Rausher leukemia virus was observed, as virus titers in the plasm of mice with marked stimulation or inhibition of splenomegaly were identical and did not differ from those in mice without Trichinella spiralis invasion.

Analysis of the Kinetics of the immune response by means of ionizing radiation.

The inhibitory kinetics of the primary immune response was studied by means of lethal irradiation. CBA mice were immunized with sheep red blood cells and 48, 72 and 96 hours later, they were irradiated with 750R. Afterwards, the number of direct plaque-forming cells was determined in their spleens during 58 to 66 hours at 4-hour intervals. After irradiation at 48 and 72 hours of the immune response, a plateau of different duration was obtained: 48 hours in the former and 24 hours in the latter case. In both cases, reduction in the PFC number began at about 96 hours of the resonse. The PFC reduction curves in these two series of experiments and those obtained 96 hours after irradiation and in control, non-irradiated mice were parallel. The mean half-time of the PFC number reduction as determined by these curves was 6 hours. The time of functioning of PFC in the spleen is discussed with respect to recruitment of proliferating precursors.