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In the use of colostral protective factors and insufficient activity of piglets immune system, against the background of immunodeficiency after weaning from sows developing diseases, often caused by conditionally-pathogenic or pathogenic microorganisms, including non-contagious gastroenteritis. The article presents analyzes of T- and B-cell immunity parameters in weaned piglets with non-contagious gastroenteritis and after their treatment with probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930 as part of the basic diet in combination with antibiotic (10 % solution of enrofloxacin hydrochloride) in the modern pig farm. It was established that in piglets after weaning with non-contagious gastroenteritis decreased of T- and B-cell immunity parameters. In particular, in blood decreased number of total and active T-lymphocytes, T-helpers and T-suppressors also decreased number of B-lymphocytes, which may indicate the development in these immunodeficient condition. It was established positive effect of probiotic and phytobiotic in combination with antibiotic on T-cell immunity of pigs, as indicated by the increased number of total T-lymphocytes in blood to the clinical healthy animals level. A similar tendency was observed in the number of T-helper cells, their number was higher in groups of weaned piglets which added probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930. As to the immunoregulatory index, which is a quantitative ratio of T-helper to T-suppressor, there was no significant alteration of values in control and experimental groups of pigs. It was established positive effect of probiotic and phytobiotic in humoral immunity of piglets by increasing number of B-lymphocytes to the level of clinical healthy animals which indicate increased body ability to the active synthesis of protective antibodies. The use of probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930 for weaned piglets with non-contagious gastroenteritis normalized number of T- and B-lymphocytes, which are the leading immunocompetent blood cells that characterize the level of animal body defense and condition of specific immunity. Perspectives for further research will be directed at determining the therapeutic effectiveness of probiotic TOYOCERIN 10⁹ and phytobiotic EXTRACT™ 6930 for weaned piglets with non-contagious gastroenteritis.

What are the minimum specificity requirements of a thymic selective process that establishes (1) restrictive recognition of peptide, (2) the Self (S)-Nonself (NS) discrimination, and (3) the categories of effector function? Given an answer to that question, how well does it fit with the observed selective processes in thymus where T-cells are generated? Any discrepancies between the two must be rationalized. The goal of this essay is to attempt just that.

Introduction The revised QuantiFERON-TB Gold assay (QFT-Plus) has an extra tube (TB2), containing peptides thought to stimulate CD8 +T cells; TB7 antigen is no longer included. The test is designed to detect latent tuberculosis infection. Hypothesis Levels of interferon-γ in TB2 should always be greater than TB1 Methods QFT-Plus was used routinely in a TB contact clinic June 2016 – January 2017. Interferon-γ values were recorded minus the negative control; a significant difference was defined as a two-fold variation. Clinical details were recorded after consent on a standard form, which included age, sex, reason for test, tuberculin response (mm) and HIV status. Results Data was available from 259 subjects; 2 were HIV-positive. Four gave an indeterminate result. The majority (194; 75%) gave a negative test for both tubes. For 65 positive tests with a≥2 fold difference (all ≥0.7 IU/mL difference), TB1 ≥TB2 occurred in 4 (6%) and TB2 ≥TB1 occurred in 3 (5%). All 4 TB1 ≥TB2 had no TB2 response: there were 2 contacts (10 and 0.68 IU/ml); one was PPD positive with neck lymphadenopathy (4.23 IU/ml); one was PPD negative with haemoptysis after nasal surgery (1.75 IU/ml). Where TB2 was positive in the ‘grey zone’ and TB1 negative, one had Crohn’s disease (0.24, 0.01 IU/ml) and the other (0.23, 0.01 IU/ml) was a contact of non-pulmonary TB, but in none was there HIV co-infection. Three had TB2 ≥TB1: one with smear-positive lung TB had a TB2=0.6 with a TB1=0.25, but the latter was in an accepted ‘grey zone’; two had positive tests for both tubes, of which one was a contact 30 years previously and one had testicular TB. Conclusion These data may indicate a technical failure of the TB2 tube. Alternatively, the absent immune response, associated with active disease, might prove useful in determining who could benefit from preventive treatment.

Any discussion of the regulation of effector class must include feedback control on the magnitude of the response. The induced effector activities are biodestructive and ridding. They are, in and of themselves, unspecific with respect to self and nonself. Consequently all responses include some level of innocent bystander pathology. The regulation of magnitude is essential to keeping this level of pathology at an evolutionarily acceptable level. This is my postulated role of suppressor T-cells, more popularly referred to as Treg. In order to perform this function they must be somatically selected to be anti-nonself like all other T/B-cells. If correct, any role that they might play in determining normal tolerance is excluded. As the commentary of Ellestad illustrates, their function to regulate autoimmunity is the consensus view today and, therefore, this competing concept and my analysis of suggested papers should invite a wide ranging debate.

Recent experimental studies have suggested the ratio between T-helper and T-suppressor lymphocytes as an index of immunosuppression in HIV, cancer, immunosenescence and inflammatory and auto-immune diseases. However, a quantitative understanding of the impact of this ratio on the immune response has lagged behind data and its validity as a tool for prognostic monitoring or therapeutic target remains an open question. In this work, we use statistical physics and dynamical systems approaches to analyze the time-dependent response to an antigen, of a simplified model of the adaptive immune system, which comprises B, T-helper and T-suppressor lymphocytes. The model is remarkably robust against changes in the noise level and kinetic parameters, but it is very sensitive to changes in the ratio between T-helper and T-suppressor lymphocytes, exhibiting, in particular, a transition from a responsive to an immuno-suppressed phase, as the ratio is lowered below a critical value, which is in line with experiments. This result supports the validity of the T-helper/T-suppressor ratio as an index of immunosuppression and may provide a useful theoretical benchmark to interpret and compare experiments., 22 pages, 11 figures

T cell subpopulations were determined in 88 Swedish patients with severe hemostatic disorders treated with domestic or imported American factor VIII or Swedish factor IX preparations at two centres, Karolinska hospital (KH) and Malmo hospital (MH). Among the patients with severe hemophilia A from KH, all of whom had received American factor VIII concentrate, a decreased T helper/T suppressor (Leu 3/Leu 2) cell ratio (below 0.8) was found more frequently in adults (8 of 10) than in children (1 of 10). In the study of patients from MH, 15 of 18 adults and 4 of 8 children with severe hemophilia A, who had been treated with American factor VIII concentrate, had a decreased Leu 3/Leu 2 cell ratio. Decreased T cell ratios occurred also in hemophiliacs treated only with concentrates of Swedish origin. Thus 3 of 5 adults and 1 of 10 children with severe hemophilia A treated with Swedish factor VIII preparations (usually fraction 1-0) as well as 2 of 8 adult hemophilia B cases treated with Swedish factor IX concentrate had a ratio below 0.8. There was no relationship between the T cell ratio and the amount of factor VIII of American or Swedish origin (expressed in units per kg and year) received during the previous two years.

We have studied immune regulation in MS using monoclonal antibodies against T cell subsets.We could confirm a decrease in the number of T suppressor cells in peripheral blood of 16 active MS patients (16.7%±1.7) when compared to 16 healthy controls (26.2±2.2 p

Arriving at an understanding of the role of suppressor T-cells (regulatory T-cells, CD4 + CD25 + ) depends on whether their functional repertoire is somatically selected to be anti-Self or anti-Nonself. Immunologists are ambivalent; often publications espousing opposite views share an author. Here the arguments are detailed that the suppressor repertoire is not somatically selected to be anti-Self, but rather it is anti-Nonself. Therefore, suppression cannot regulate the Self–Nonself discrimination; its function is to regulate the magnitude and class of the anti-Nonself effector response.

Regulatory T cells are shown to originate form the thymus and their role is to maintain self-tolerance to intra-thymic as well as extra-thymic self-antigens. Their mode of action, using in vivo and in vitro systems, has led to different conclusions as to the need of cell–cell interactions or regulation upon suppressive cytokines. The more we study regulatory T cells the more we find similarities to the old notion of the suppressor T cell network. The limited knowledge in molecular technology in the early 70s and 80s discouraged investigators to further scrutinize the issue and the terms T suppressors and contra-suppressors that were coined back then have been forgotten over the years. It is now time to remember the work of these investigators and attempt to explain their findings using the current knowledge and technology.

Here we present a comparative temporal analysis of the appearance and dynamics of cytogenetic and immune activity of lymphocytes during regenerative processes in different organs based on own and published data. The changes in these activities are coupled and codirected, depend on experimental conditions, but are realized via different pathways. These similarities depend on changes in the balance between immunoregulatory cells (T helpers and T suppressors).

Three inoculations of live and inactivated Ebola virus to susceptible (guinea pigs) and resistant (rabbits) animals helped reveal some regularities in the immunity reactions which have not been observed after a single inoculation: an increase in the count of T suppressors both in rabbits and guinea pigs after reinoculations of the virus preparations and the resistance of T lymphocytes in rabbits and their suppression in guinea pigs. Similar immunogenicity of live and inactivated Ebola virus for guinea pigs and a higher immunogenicity of live virus for rabbits deserves attention.

I have briefly reviewed the factors that motivated me to change my views about the existence and importance of suppressor/regulatory T cells and to devote the majority of my laboratory efforts to this newly revitalized area of immunologic research. I am optimistic that manipulation of regulatory T-cell function will shortly be applicable to the clinic.

Race, age, sex, and environmental conditions have significant impacts on lymphocyte subset values. It is important to establish the local reference ranges from healthy and non-HIV-positive adults in the local population for clinical decision making. In this study, the reference ranges for lymphocyte subsets among Chinese adults were established by analysis by single-platform flow cytometry of the lymphocyte compositions of 273 healthy adult blood donors between 17 and 59 years of age. The 95% reference ranges for CD3 + T cells, CD3 + CD4 + T helper cells, and CD3 + CD8 + T suppressor cells are 723 to 2,271 cells/μl, 396 to 1,309 cells/μl, and 224 to 1,014 cells/μl, respectively. The 95% reference ranges for CD19 + B cells and CD56 + NK cells are 118 to 645 cells/μl and 61 to 607 cells/μl, respectively. Significant gender and age differences in the lymphocyte subsets have been demonstrated. Our results have also shown that the T-lymphocyte compositions in Hong Kong Chinese were comparable to those of other Asian populations but were different from those of Caucasians.

We investigated the cellular induction mechanism of antigen-nonspecific CD8 + T suppressor cells which suppressed delayed-type hypersensitivity to sheep red blood cells, by treating BALB/c mice with 7,12-dimethylbenz[ a ]anthracene (DMBA), a tumor initiator, and 12- O -tetradecanoylphorbol 13-acetate (TPA), a tumor promoter. Macrophages were activated by painting with 400 nmol of DMBA on mice. And the macrophages plus TPA induced CD4 + T suppressor inducer cells in the mice spleens. These cells were efficient at inducing CD8 + T suppressor–effector cells. When 8 nmol of TPA was painted daily on mice for 3 days following the treatment with 400 nmol of DMBA, or when spleen cells from mice pretreated with 400 nmol of DMBA were cultured in 32 nmol/5 ml of TPA for 3 days, inducer cells were formed in the spleen. Both T suppressor–inducer cells and macrophages from mice treated with DMBA were shown to act with the formation of soluble factors, which may be different from IL-10.

Irradiation of pregnant mice causes destruction of the embryonal thymus and delays its colonization with lymphocytes, T-helper maturation, and elimination of T-lymphocyte precursors. After birth splenic colonization with lymphocytes, particularly with T helpers and T suppressors, is decresed.

The influence of ganglioside GM3 and some of its breakdown products on phytohemagglutinin-induced blast transformation of human lymphocytes and concanavalin-A-induced T-suppressor activity was studied. The structures of two major hydrolysis products of GM3 were established by negative-ion fast-atom-bombardment mass spectrometry as neuraminyllactosylsphingosine (NeuLacSph) and neuraminyllactosylceramide (NeuLacCer). Both substances were shown to be potent inhibitors of mitogen-induced lymphoblastic transformation whereas their acetylation products NeuAcLacSphAc and GM3 did not affect the proliferative response of lymphocytes to phytohemagglutinin. On the other hand, only GM3 and NeuLacSph were able to enhance concanavalin-A-induced T-suppressor activity. On the basis of these data, it is suggested that the effects of GM3 and its breakdown products on lymphoblastic transformation and T-suppressor activity must rest on different mechanisms and that N-deacylation of GM3 appears to be an essential step in conversion of the ganglioside into an inhibitor of lymphocyte blast transformation.

The leukemia-associated autoinhibitor (LAI-615) derived from murine leukemia L7811 has been investigated intensively in our laboratory. In the following experiments, the partial purification of LAI-615 has been carried out in addition to the observation of phenotype variations of L7811 leukemic cells. The factor was purified over 1306-fold by sequential fractionation with Sephadex G-150 gel filtration, DEAE-cellulose ion exchange chromatography, and Mono Q-fast protein liquid chromatography. The molecular weight of LAI-615 was 68,000 as estimated by gel filtration. LAI-615 was a protein but not glycosylated, and it was suggested LAI-615 be secreted in an autocrine manner. Immunocytochemical staining showed that the expression of Lyt2 phenotype of L7811 leukemic cells was often coincident with the secretion of LAI-615. Moreover, the physicochemical characteristics of LAI-615 was similar to that of T suppressor factor. Thus it is concluded that LAI-615 may be one of TsF-like factors.

The expression of I-A antigen in rat peritoneal cells was significantly reduced during infection with Cryptococcus neoformans. When studying the in vitro action of T-suppressor cells induced by the fungus, or a soluble factor from the T-suppressor cells, a significant decrease in I-A expression by the peritoneal cells was observed. This expression was partially restored by indomethacin.

The percent and absolute content of T helpers increases in the spleen of mice 4 and 17 h after resection of the liver or removal of a kidney, which is associated with an increase of the mitotic index of splenocytes. The number of T suppressors and the bone marrow cell mitotic index are unchanged. The T-helper/T-suppressor ratio in the spleen increases 1.7–2 times during surgery on the liver and kidney.

Effects of chorionic gonadotropin (CG) on the functional activity of antigen-specific T-suppressors generated in CBA mice on day 14 by supraoptimal dose of thymus-dependent antigen were studied. The activity of T-suppressors was assessed by the level of antibody-producing (ABP) cells forming in the organism of suppressor cell recipients immunized with the same antigen. CG was injected to intact and oophorectomized recipient mice or was directly incubated in a one-hour cell culture with antigenspecific suppressor cells which were then transplanted to intact female mice. CG in a dose of 40 or 200 IU did not influence the capacity of T-suppressors to suppress primary immune response in intact females. In oophorectomized animals the hormone statistically reliably decreased the activity of T-suppressors, no matter what its dose were, and depressed the splenocyte activity. In a cell culture CG similarly depressed T-suppressor functional activity without influencing their homing.

Group A streptococcus polysaccharide is found to inhibit the activity of ConA-stimulated T suppressors. A-variant streptococcus polysaccharide, representing an L-rhamnose homopolymer which is identical to the rhamnose carcass of group A streptococcus polysaccharide, does not possess such an effect. The effect of group A streptococcus polysaccharide on the activity of T suppressors is considered to be associated with its determinant including N-acetylglucosamine as an obligatory component.

OBJECTIVE: Our goal was to analyze interactions of lymphocytes in peripheral blood and thyroid tissue in children with Graves' disease (GD). METHODS: The prospective study concerned 15 children affected with GD and 15 healthy children. The levels of autoantibodies against thyrotropin receptor, thyroid peroxidase, and thyroglobulin were assayed. Monoclonal antibodies (Ortho Diagnostic Systems, Raritan, NJ) were used to define peripheral blood lymphocyte subsets and analyzed by using a flow cytometer. After thyroidectomy, thyroid specimens were stained with hematoxylin/eosin. T cells were detected by CD3+, CD4+, and CD8+ antibodies and the antigen-presenting dendritic cells with CD1a+ and CD35+ antibodies (DakoCytomation, Glostrup, Denmark). RESULTS: Before treatment, all children with GD had increased thyroid autoantibody levels, an increased percentage of CD4+ helper cells, and decreased levels of CD8+ suppressor/cytotoxic T cells, which resulted in an elevated CD4/CD8 ratio. The percentage of CD19+Cd5+ B cells was increased, although the total population of CD19+ B cells did not differ from that of the control group. The number of lymphocytes in the thyroid was decreased in 10 patients after long-term thiamazole treatment. In 5 patients with short-term therapy ( CONCLUSIONS: The primary defect of immunoregulation in GD consists of an increase of T-helper lymphocytes with a simultaneous decrease in the number of T-cytotoxic/suppressor cells. Thiamazole therapy probably leads to reduction of the lymphocyte amount in the thyroid.

A set of CTL-lines in the system differing in the whole H-2 complex, as well as in distinct subregions of H-2, was established. These lines were routinely tested in Cr 51 -release assay to insure that they retained lytic activity and antigen-specificity. The result of the interaction of CTL with H-2K b -molecule and α 1 -thymosine was transition of CTL into a reversible state of anergy. A high concentration of α 1 -thymosine is necssary for this transition. Anergic CTL caused specific suppressor activity that is functional if transformation of CTL into T-suppressors took place.

This study investigates the T lymphocyte role in the production of the specific immunosuppressive environment that occupies the anterior segment of the eye. Aqueous and peripheral venous blood samples were taken from 23 patients who were operated because of senile cataract. In all samples, T helper/T suppressor ratios were established and differences between aqueous and blood samples were investigated by t statistic and Mann-Whitney U test. We found significantly more T suppressor cell activity in aqueous humor than in peripheral blood (p0.05). We think that high T suppressor concentration in aqueous humor plays an important role in the induction of the immunosuppressive microenvironment that occupies the anterior chamber of the eye.

T cell subsets and immunoglobulin (Ig) were observed sequentially with the OKT monoclonal antibodies rosette test and the rate scattering turbidimetry in 13 patients who underwent open heart surgery under cardiopulmonary bypass (CPB) for rheumatic heart diseases (RHD) and congenital heart diseases (CHD), before and after operation. Compared with preoperative values, in the early period after CPB, T helper cells, T helper cells to T suppressor cells ratio and IgG decreased significantly; whereas T suppressor cells increased, in RHD and CHD. The T cell subsets returned to the preoperative levels two weeks after CPB in RHD and CHD. The IgG came back to the preoperative levels two weeks after CPB in RHD and only one week after CPB in CHD.

A close analysis of clonal anergy and T suppressor systems reveals a considerable overlap between these two phenomena in experimental conditions. While evidence accumulates in favour of anergy in the maintenance of self-tolerance and in experimental manipulations, the concept of antigen-specific T cell suppression coupled with the conventionally attributed features of T suppressor cells remain as an enigma. This has lead to a widespread scepticism and controversies. Hence synthesis of a theory to explain and (better) understand antigen-specific suppression becomes an essential task in basic immunology. In the present article the phenomenon of clonal anergy is subdivided, theoretically, into three states and then analysed in the context of different experimental systems. it is suggested that partially anergic cells, termed as state 3 cells, can be the effectors of antigen-specific suppression.

Pregraft transfusion combined with immunosuppression at the time of grafting improves the survival of clinical and experimental allografts. The mechanisms responsible for this effect were investigated in the murine model of cardiac transplantation, combining transfusions 7 to 30 days prior to transplantation with cyclosporine 100 mg/kg, 7 to 20 days pregraft or on days 0, 4, and 6 after grafting. Pregraft DST, third-party blood, and CsA all improved graft survival in the BALB/c-to-CBA donor-recipient combination. In animals treated with DST at 14 days pregrafting, 4/9 grafts survived for greater than 100 days. In those given C57BL/6 blood, or CsA on days 0, 4, 6 postgraft, 1/9 grafts survived for greater than 100 days. When 10(7) spleen cells from DST-treated CBA mice with long-surviving BALB/c heart grafts were transferred to naive CBA mice that then received a BALB/c heart 24 hr later, the transferred cells prolonged graft survival, with all grafts functioning at greater than 40 days, and 4/7 at greater than 100 days. Selective removal of T cells from the spleen cell population prior to transfer showed that L3T4+ T cells, but not Ly-2+ T cells, were required to maintain BALB/c allografts. Combining a short course of CsA with DST was more effective than either treatment alone. The most effective combined treatment was DST at day -14 with 100 mg/kg CsA given on days 0, 4, and 6 postgrafting (8/10 grafts survived greater than 100 days). This treatment also induced splenic suppressor T cells of the L3T4+ Ly-2- phenotype. These results clearly show that L3T4+ splenic T suppressor cells are induced by donor-specific blood transfusion with or without CsA treatment, and that these cells play a role in maintaining long-term tolerance to allografts in the mouse heart transplant model.