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Studies on the regulation of lymphocyte production in the murine thymus and some effects of a crude thymus extract.

Cell proliferation in the murine thymus was studied in vivo under normal conditions and from 0 to 24 hr after a single injection of a water-soluble extract from mouse thymus, mouse spleen, and mouse skin. The thymus extract reduced during the first 24 hr the mitiotic activity 40%; the spleen extract had a weaker inhibitory effect. The skin extract had no such effect. The thymus extract and spleen extract inhibited the flux of cells into the S phase 0-8 hr after the injection of the extract. Initial labelling index was also reduced in this period. Eight hours after injection of the thymus or spleen extracts the inhibited cells initiated DNA synthesis. The rate of progression of blast cells through the cell cycle was normal 24 hr after the injection of the extracts. It was deduced from the analysis that the thymus extract inhibits processes triggering G0/G1 cells into DNA synthesis, the inhibition of G2 efflux being of minor importance. Finally a model for the regulation of proliferating thymic blast cells and the emigration of small lymphocytes from the thymus is proposed.

Animals

Initial observations on the administration of thymus extract (TFX) in patients with alimentary tract neoplasms.

The administration of thymus extract (TFX) has been performed in 35 patients suffering from malignancies of the alimentary tract. TFX, being a calf thymuses extract prepared by Jelenia Góra Drug Producers "Polfa" was given in the dose of 0.5 mg in 3 or 7-day intervals during several months. The immunological condition of patients was checked by many tests: E-rosettes, DLT (direct lymphocytotoxicity test) determination of absolute number of peripheral blood lymphocytes and skin tests (RT-23, PHA and TFX). Our observations revealed that TFX is biologically active also in humans, increases cell-mediated immunity and may restore the immune capability of patients operated due to malignancies of the alimentary tract.

Adult

[Restoration of antibody synthesis by means of thymus extract in neonatally thymectomized animals].

One of the fractions of the thymus extract of a calf obtained by the authors restored the synthesis of antibodies to sheep erythrocytes in neonatally thymectomized mice and rats. Fractions isolated anologously from the tonsils and the lymph nodes failed to influence the antibody genesis. The data obtained are in favor of the endocrine function of the thymus of significance in the establishment and regulation of the immunological reactivity.

Animals

A hypocalcemic and lympnocyte-stimulating substance isolated from thymus extracts, and its physicochemical properties.

Two kinds of active protein fraction, TP1 and TP2, were isolated from bovine thymus extracts. Both these fractions showed a single band in polyacrylamide gel disc electrophoresis. Though these two fractions showed a difference in potency, they both lowered serum calcium in rabbits and increased lymphocytes in mice. Molecular weight determination by SDS polyacrylamide gel electrophoresis gave the values of 68,000 for TP1 and 57,000 for TP2. Amino acid composition of TP1 did not show marked characteristics but was clearly different from that of bovine serum albumin. Isoelectric focusing showed the isoelectric point at pH 5.65 for TP1 and pH 5.4 for TP2. Dose-response relation in serum calcium-lowering activity was examined with a sample purified from the extracts, and a linear dependence of the response to log dose was recognized over a moderate range of doses. The time-course measurement of the hypocalcemic activity showed that the action of TP1 is somewhat different from that of calcitonin.

Amino Acids

Activation of T and B lymphocytes in vitro. IV. Regulatory influence on specific T cell functions by a thymus extract factor.

In the presence of a preparation of purified thymus extract factors (TEF), spleen cells from athymic nude mice develop in vitro immune responses to soluble DNP-protein conjugates, to particulate sheep red blood cells, and to allogeneic cells. TEF has similar effects also on the in vitro antibody responses of normal mouse spleen cells, enhancing antigen-dependent plaque-forming cells responses to dinitrophenyl carrier complexes of unprimed and primed mice. TEF fails to reconstitute helper cell function in cultures of T cell-deprived spleen cells. The thymic factor increases the reactivity or normal thymus cells in the in vitro mixed lymphocyte reaction and has at high doses mitogenic effects. The role of humoral thymus factors on the differentiation process of T cells is discussed.

Animals

[Effect of thymus extract and late thymectomy on interferon generation].

No production of interferon was observed in ten-day mice in response to the injection of the Newcastle disease virus. Single injection of the calf thymus extract fraction obtained by the method of Gujlling et al. to newborn mice induced the capacity of interferon genesis in the animals at the age of ten days. Adult rats produced interferon in response to Newcastle disease virus. The intensity of interferon synthesis was unaltered 2 to 3 months after thymectomy.

Animals

Adult thymectomy prevention of the appearance of suppressor T cells which depress contact sensitivity to picryl chloride and reversal of adult thymectomy effect by thymus extract.

Suppressor cells, which depress the passive transfer of contact sensitivity appear in the lymph nodes and spleen of mice injected with picryl sulfonic acid (PSA). These cells produce a soluble suppressor T cell product (s-TCP), and immune lymph node cells incubated in s-TCP fail to transfer contact sensitivity. This paper shows that the appearance of suppressor T cells following the injection of PSA was prevented by adult thymectomy (ATx). ATx also limited the production of s-TCP. However, ATx had no effect on the DNA synthesis which occurs in the lymph nodes of mice injected with PSA. The adverse effect of ATx on suppressor cells was completely reversed by a neonatal thymus graft placed under the renal capsule and partially reversed by grafts given 600 r in vitro and to a limited extent by grafts given 1000 r. The injection of thymus extract also reversed the effect of ATx whereas splenic extract was inactive. It is suggested that the suppressor T cell which depresses contact sensitivity is dependent on the presence of the thymus because it requires a thymus hormone, and not primarily because it belongs to a short-lived population which is rapidly renewed by cells coming from the thymus.

Animals

The in vitro effect of a calf thymus extract on the peripheral blood lymphocytes of sixty-six melanoma patients.

The in vitro effect of a calf thymus extract (TP-1) on peripheral blood lymphocytes was evaluated in sixty-six melanoma patients. Twenty out of forty-five stage I and seventeen out of twenty-one stage IIb patients presented depressed T lymphocyte values. A statistically significant increase in E-rosette-forming cells (E-RFC) was observed in seventeen (85%) stage I and twelve (70.5%) stage II patients. In thirteen (65%) stage I and eight (47%) stage II patients E-RFC reached normal values. Our results indicate that the fall of T lymphocytes in the peripheral blood of melanoma patients is often related to an increase in TP-1 sensitive cells which suggests the possibility of a thymic hormone deficiency in these patients.

Adult

[Effect of calf thymus extracts on the surface structure and the lysosomal apparatus of lymphocytes in patients with chronic lymphatic leukemia].

In 6 patients with chronic lymphatic leukaemia receiving subcutaneously purified calf thymus extract a greater frequency of the following processes was observed: 1) increase in the number of smooth-surface lymphocytes (T cells) in scanning electron microscopy, 2) increased number of lymphocytes forming rosettes with uncoated sheep erythrocytes, 3) increased number of lymphocytes showing high activity of acid phosphatase in cytochemical investigations.

Acid Phosphatase