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PubMed1979

Studies of T lymphocyte function and inhibitory factors in minimal change nephrotic syndrome.

Plasma obtained from patients with MCNS in active stage suppressed the 3H-TdR incorporation of autologous or homologous lymphocytes stimulated with PHA-P and E rosette formation, while plasma from patients in remission did not. The depressed mitogenic response of lymphocytes from patients in the active stage significantly improved when the patient's plasma was substituted for the plasma from inactive MCNS or healthy persons and fetal calf serum. In the preliminary experiment, it was seen that the inhibitory factors were heat stable at 56 degrees C, unadsorbable to charcoal powder and retained in both the permeable and impermeable fractions of collodion bag.

Humans↗
PubMed1978

Regulation of lymphocyte proliferation by soluble products released by stimulated human lymphocytes.

Human lymphocytes pulsed with phytothaemagglutinin (PHA) release mitogenic factors and other lymphokines upon subsequent incubation in fresh medium. Such active supernatants (SUPs) were assayed for their capacity to modify the DNA synthetic response of human lymphocytes exposed to various mitogenic stimuli. Both non-fractionated peripheral lymphocytes and preparations of fractionated T cells were stimulated by active SUPs to DNA synthesis. In contrast, active SUPs reduced the responses of lymphocytes to allogeneic cells, PPD tuberculin and PHA. These reductions were most evident at the end of the culture periods. The results suggest that soluble products released by stimulated lymphocytes activate suppressor lymphocytes which inhibit proliferative responses of lymphocytes.

Humans↗
PubMed1979

Characterization of lymphocytes which inhibit proliferation of human T cells exposed to lymphocyte-derived mitogenic factors.

Culture supernatants of PHA-activated human lymphocytes (active SUPs) contain factors which are strongly mitogenic for fractionated peripheral T cells. This stimulation is suppressed by certain non-T lymphocytes. It is shown that these suppressor cells can inhibit an ongoing response of T cells to active SUP and that this inhibition is reversible. Using various rosette sedimentation techniques for fractionating subpopulations of lymphocytes it is concluded that the suppressor cells lack membrane-associated receptors for C3 but possess receptors for the Fc part of IgG. This subset of lymphocytes may be an important regulator of lymphocyte proliferation during immune responses.

Adult↗
PubMed1979

Differences in flow cytometry and 3H-thymidine analyses of perturbed human lymphocytes.

A calf thymocyte crude aqueous extract was tested for DNA synthesis inhibitory activity using phytohemagglutinin-stimulated human peripheral blood lymphocytes. Inhibition of DNA synthesis was assayed using tritiated thymidine and flow cytometry. Although the calf thymocyte crude extract inhibited tritiated thymidine incorporation by over 50%, only very slight changes in the flow cytometric analysis were observed. When dibutyryl-cyclic adenosine monophosphate was used as an inhibitor, a correlation in terms of the inhibition of tritiated thymidine to the inhibition by flow cytometry was observed.

Animals↗
PubMed2026

Natural killer (NK) cells with downregulated activating receptors and IL-10 production promote Trypanosoma cruzi T-cell responses in subjects in the Chronic phase of Trypanosoma cruzi infection: An exploratory immunological analysis.

BACKGROUND: Subjects with chronic Chagas disease and no signs of heart disease exhibit decreased NKp46 expression, high CD57 expression, and IL-10 production by NK cells. This study provides a detailed characterization of the phenotype and function of NK cells according to the severity of heart disease, and evaluates how these changes following treatment with benznidazole, as well as their association with Trypanosoma cruzi-specific T-cell responses. METHODS: The phenotype and function of NK cells in a cohort of 51 subjects infected with Trypanosoma cruzi and exhibiting varying degrees of heart disease were evaluated using high-dimensional flow cytometry and Boolean gating analysis. ELISPOT assays were performed to measure IFN-γ and IL-2 production in response to T. cruzi antigens, using CD56, CD4 and CD8-depleted PBMC. RESULTS: In contrast to individuals without heart disease, those with advanced cardiomyopathy have an increased number of NK cells that express the activating receptors NKp46 and CD16, as well as the differentiation marker CD57. NK cells in subjects with advanced cardiomyopathy were also found to be enriched in CD56+CD107+granzyme B+TNF-α+ cells and depleted of CD56+IL-10+ cells. The function of NK cells shifted towards monofunctionality in subjects with declining T. cruzi-specific antibodies following treatment with benznidazole. Eliminating CD56+ cells significantly decreased the number of IFN-γ-producing cells in response to T. cruzi. CONCLUSIONS: In chronic T. cruzi infection, NK-cell function may be balanced by the downregulation of activating receptors and IL-10 production, However, parasite persistence may desensitize the regulation of NK activating receptors, enabling NK cells to exert a potent polyfunctional cytotoxicity that potentially induce tissue damage.

Humans↗
PubMed1978

Mitogenic factor from chronically infected guinea pigs.

A lymphokine produced by antigen stimulated lymphocytes, induces blastogenesis in cultures of lymphocytes which are not sensitive to the specific antigen. The in vitro production of this factor (MF) was accomplished utilizing peritoneal exudate (PE) cells from Coccidioides immitis infected guinea pigs. Production of MF by lymphoid cultures paralleled skin test reactivity of the donor animal. Removal of adherent cells from the PE population did not decrease the production of MF; conversely, a more significant production of MF was effected by the adherent cell depleted populations. Maximal production of MF was achieved at non-adherent cell concentrations from 4 X 10(6) to 8 X 10(6) cells/ml. Cell concentrations below 4 X 10(6)/ml produced material which inhibited DNA synthesis in test cultures. MF was separated from the inhibitory substance(s) by column chromatography of the crude preparations on Sephadex G-75. Inhibitor(s) eluted in the void volume (VO), and the MF eluted in an effluent volume (Ve) which was greater than the total bed volume (Vt) suggesting that MF is adsorbed by Sephadex beads.

Animals↗
PubMed1979

Catheptic carboxypeptidase B as a major component in "T-cell activating factor" of macrophages.

TAF (T-cell activating factor), produced by peritoneal macrophages and assayed by its ability to potentiate DNA synthesis in macrophage-depleted lymph node cells stimulated with Phytochemagglutinin-concanavalin A, was shown to contain catheptic carboxypeptidase B (CPB) which accounted almost quantitatively for its potentiating activity. TAF action was inhibited by CPB inhibitors and could be mimicked by commercial pig pancreas CPB. The activity was absorbed from active supernatants on EACA-Sepharose and could be eluted with free EACA (epsilon aminocaproic acid).

Animals↗
PubMed1978

[Origin of a mitogrenic factor for cultivated macrophages (IMF: Inflammatory Mitogenic Factor) found in exudates of non-specific acute inflammation].

The mitogenic activity of inflammatory exudate obtained from irradiated Rats is reduced. After transfer of bone marrow syngeneic cells into irradiated Rats this mitogenic activity is further decreased, while after transfer of thymic cells it is increased. It is postulated that the mitogenic activity of inflammatory exudate could be related to thymic cells and that T lymphocytes may be involved in non specific-inflammatory reactions.

Acute Disease↗
PubMed1979

Role of endothelial injury and platelets in atherogenesis.

Endothelial cell injury is usually followed by the adherence and activation of platelets to exposed subendothelial surfaces. This is then followed by intimal smooth muscle cell proliferation and formation of connective tissue matrix by the smooth muscle cells through synthesis and secretion of collagen, elastic fiber proteins, and proteoglycans, and intracellular and extracellular lipid accumulation. Platelet activation is associated with morphological transformations which lead eventually to the "release reaction". A mitogenic factor has been recently recognized among the substances released from platelets and it may play a crucial role in promoting the intimal proliferation of smooth muscle cells which characterize atherosclerotic plaques.

Animals↗
PubMed1977

Lymph node activating factor from mixed cultures of allogeneic lymphoid cells: effect on the lymph nodes of euthymic and athymic mice.

The action of "lymph node activating factor" (present in supernatants from 4hr cultures of allogeneic lymphocytes) on the lymph nodes of athymic nu/nu mice, nu/+ hybrids and euthymic BALB/c mice was studied. An increase in lymph node weight, cellularity and changes in lymph node morphology, i.e. an increase of the dense lymphatic tissue of the cortex and paracortex and appearance of follicles with light centers, were found in all mice. Lymphocyte activation evaluated by the presence of lymphocytes with RNA synthesizing nucleoli occurred only in nu/nu mice and nu/+ hybrids. Marked changes in lymph node morphology found in nu/nu homozygotes suggest relation of the lymph node activating factor to mediators acting directly on B cells.

Animals↗
PubMed1978

The appearance of factors influencing migration of lymphocytes (LyMIF and LyMSF) in rabbit mixed lymphocyte cultures.

In vitro migration of mixtures of peripheral blood lymphocytes derived from 26 pairs of rabbits was significantly suppressed in 73% of cultures, significantly enhanced in 4% and unchanged in 23%, as compared to the corresponding monocultures. Sensitization of 26 rabbits by kidney graft resulted in more frequent appearance of migration enhancing factor. Six days after grafting 54% of donor-recipient mixed cultures showed enhancement of migration, 31% inhibition and 15% no effect. No enhancing factors were produced on the 9th day.

Animals↗
PubMed1977

In vitro cell response of Treponema pallidum-infected rabbits. III. Impairment in production of lymphocyte mitogenic factor.

Production of mitogenic factor was examined in rabbits infected intratesticularly with T. pallidum and in control animals injected with saline or saline extract of normal rabbits' testes. Lymph nodes and spleen from animals killed 2, 6 and 12 weeks after injection were used as the source of lymphocytes, cultured in serum-free medium in the presence of Reiter antigen. The active supernatants of lymph node cells (LNAS) and spleen cells (SPAS) were examined for the presence of mitogenic factor using normal rabbit peripheral lymphocytes. The LNAS of control animals showed a mitogenic index (MI) between 4 and 6 and the infected animals less than 2. The SPAS of infected and control rabbits showed an MI of less than 2. The lower mitogenicity in LNAS of infected and that of SPAS of infected and control animals seems to be due to the presence of inhibitors of DNA synthesis.

Animals↗