scholarly journals SEMAPHORIN 3A - A NEW INTRATHYMIC SUPPRESSOR FACTOR

2019 ◽  
Vol 19 (1S) ◽  
pp. 203-205
Author(s):  
K V Rutto ◽  
E P Kisseleva
Keyword(s):  
Immune Responses ◽  
Axon Guidance ◽  
Cell Activity ◽  
Thymic Epithelial Cells ◽  
Neuronal System ◽  
Semaphorin 3A ◽  
Therapeutic Tool ◽  
Suppressor Factor ◽  
Immunosuppressive Factor

Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several semaphorins, so-called ‘immune semaphorins’, are also involved in various phases of immune responses. One of such factors is semaphorin 3A - a member of class 3 semaphorins, which are secretory molecules in vertebrates. There are multiple mechanisms involved in the process of semaphorin 3A-mediated regulation. One of them is down-regulation of peripheral T-cell activity in consequence of which semaphorin 3A is considered as an immunosuppressive factor. But semaphorin 3A is also expressed in the thymus while its function there remains obscure. Here are discussed new data on immunosuppressive function of this factor towards thymocytes and thymic epithelial cells, obtained in vitro. Because it is involved both in physiological immunoregulation and in the pathogenesis of many autoimmune, atopic, and malignant diseases, semaphorin 3A turns to be a promising therapeutic tool to be studied and applied in these diseases.

scholarly journals Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 364 ◽  
Author(s):  
Itziar Gómez-Aguado ◽  
Julen Rodríguez-Castejón ◽  
Mónica Vicente-Pascual ◽  
Alicia Rodríguez-Gascón ◽  
María Ángeles Solinís ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasmid Dna ◽  
Messenger Rna ◽  
Insertional Mutagenesis ◽  
Gene Editing ◽  
State Of The Art ◽  
Translational Efficiency ◽  
Future Perspectives ◽  
Therapeutic Tool

The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. II. A genetically restricted suppressor of mixed lymphocyte reactions released by alloantigen-activated spleen cells.

1975 ◽  
Vol 142 (6) ◽  
pp. 1391-1402 ◽  
Author(s):  
S S Rich ◽  
R R Rich
Keyword(s):  
Immune Responses ◽  
Mixed Lymphocyte Reaction ◽  
Antigenic Specificity ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Homology Relationship ◽  
Cell Suppression ◽  
Mixed Lymphocyte Reactions

The mechanism of alloantigen-activated spleen cell suppression of mixed lymphocyte reaction (MLR) is explored in this report. Activated murine suppressor spleen cells elaborated a soluble noncytotoxic factor which suppressed MLR responses by 55-95%. Generation of suppressor factor required both in vivo alloantigen sensitization and specific in vitro restimulation. Suppressor factor was not produced by activated spleen cells which had been treated with anti-Thy-1.2 serum and complement. Antigenic specificity toward alloantigens of the stimulator cells was not demonstrable. In contrast, suppressor factor effectively inhibited MLR response only of responder cells of those strains that shared the D-end and the I-C subregion of the H-2 complex with the cells producing suppressor factor. Therefore, active suppression appears to require an MHC-directed homology relationship between regulating and responder cells in MLR.

scholarly journals Characterization of Nonpathogenic, Live, Viral Vaccine Vectors Inducing Potent Cellular Immune Responses

2004 ◽  
Vol 78 (17) ◽  
pp. 9317-9324 ◽  
Author(s):  
Jean Publicover ◽  
Elizabeth Ramsburg ◽  
John K. Rose
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cell Activity ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Wild Type ◽  
Intranasal Route ◽  
Cell Responses ◽  
Viral Vaccine

ABSTRACT Experimental vaccines based on recombinant vesicular stomatitis viruses (VSV) expressing foreign viral proteins are protective in several animal disease models. Although these attenuated viruses are nonpathogenic in nonhuman primates when given by nasal, oral, or intramuscular routes, they are pathogenic in mice when given intranasally, and further vector attenuation may be required before human trials with VSV-based vectors can begin. Mutations truncating the VSV glycoprotein (G) cytoplasmic domain from 29 to 9 or 1 amino acid (designated CT9 or CT1, respectively) were shown previously to attenuate VSV growth in cell culture and pathogenesis in mice. Here we show that VSV recombinants carrying either the CT1 or CT9 deletion and expressing the human immunodeficiency virus (HIV) Env protein are nonpathogenic in mice, even when given by the intranasal route. We then carried out a detailed analysis of the CD8+ T-cell responses, including in vivo cytotoxic T-cell activity, induced by these vectors. When given by either the intranasal or intraperitoneal route, the VSV-CT9 vector expressing HIV Env elicited primary and memory CD8+ T-cell responses to Env equivalent to those elicited by recombinant wild-type VSV expressing Env. The VSV-CT1 vector also induced potent CD8+ T-cell responses after intraperitoneal vaccination, but was less effective when given by the intranasal route. The VSV-CT1 vector was also substantially less effective than the VSV-CT9 or wild-type vector at inducing antibody to Env. The VSV-CT9 vector appears ideal because of its lack of pathogenesis, propagation to high titers in vitro, and stimulation of strong cellular and humoral immune responses.

scholarly journals Dysregulated Fas and Bcl-2 expression leading to enhanced apoptosis in T cells of multiple myeloma patients

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3679-3687 ◽  
Author(s):  
M Massaia ◽  
P Borrione ◽  
C Attisano ◽  
P Barral ◽  
E Beggiato ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Immune Responses ◽  
Cell Activity ◽  
Spontaneous Apoptosis ◽  
Activated T Cells ◽  
Ifn Gamma ◽  
Hla Dr

We have previously reported the presence of activated (HLA-DR+) T cells in multiple myeloma (MM) patients. These cells produce high amounts of interleukin (IL)-2 and interferon (IFN)-gamma and generate a potent antiplasma cell activity after appropriate in vitro stimulation, but they are unable in vivo to hold in check the disease. Activated T cells are highly susceptible to apoptosis, a form of programmed cell death involved in the modulation of immune responses and regulated by molecules such as Fas (CD95) and bcl-2. The aim of this study was to determine the expression of Fas and bcl-2 antigens and the susceptibility to apoptosis in T cells of MM patients. Fas+ cells were significantly higher, whereas bcl-2+ cells were significantly lower in MM patients than in the controls. MM patients with the highest number of HLA-DR+ T cells showed the highest Fas and the lowest bcl-2 expression. Two-color cytofluorometric analysis confirmed in individual cells that HLA-DR+ T cells coexpressed Fas and lacked bcl-2. Susceptibility to apoptosis was then investigated to evaluate the consequence of dysregulated Fas and bcl-2 expression. The percentage of apoptotic cells after incubation in medium alone (spontaneous apoptosis) or in the presence of methylprednisolone (MP) or anti-Fas monoclonal antibody (triggered apoptosis) was significantly higher in MM and mainly restricted to HLA-DR+ T cells. Spontaneous apoptotosis was reverted by exogenous IL-2. In conclusion, MM T cells have a dysregulated expression of Fas and bcl-2 antigens that is associated with an enhanced susceptibility to apoptosis. These data may unravel a novel mechanism by which activated MM T cells are weakened in their ability to exert an effective antitumor activity in vivo.

scholarly journals Mechanisms of suppression in the transfer of contact sensitivity. Analysis of an I-J+ molecule required for Ly2 suppressor cell activity.

1983 ◽  
Vol 158 (6) ◽  
pp. 1822-1835 ◽  
Author(s):  
W Ptak ◽  
R K Gershon ◽  
P M Flood
Keyword(s):  
T Cells ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Suppressive Activity ◽  
Contact Sensitivity ◽  
Suppressor Factor ◽  
Functional Activities ◽  
A Cell ◽  
Adoptive Immunity

The passive transfer of contact sensitivity (CS) by immune cells can be inhibited with an antigen-specific T suppressor factor. This factor is composed of two subfactors: an antigen-specific subfactor made by an Ly1+ cell (PC1-F) and a antigen nonspecific subfactor made by an Ly2+ T cell (TNBSA-F). The suppressive activity of the complete factor can be eliminated by depleting the assay population of Ly2+ cells, even though it is the Ly1+ cell in the population that transfers the adoptive immunity. This suggests that the Ly2+ cell in the assay population is needed to transduce the suppressive signal to the Ly1+ effector cell of DTH. We found that an Ly2+ cell from immune animals could be induced to produce a cell free subfactor that overcame the requirement for this Ttrans cell in the suppression of CS by TsF. The induction required only PC1-F, TNP-coupled spleen cells, and resulted in the production of an antigen-nonspecific I-J+ subfactor by immune Ly2+, I-J+ cells. The need for the Ly2+ transducer cell could also be overcome by addition of an I-J+ molecule secreted by Ly1 T cells hyperimmunized to SRBC. A suppressor complex made from mixing the I-J+ molecule with TNBSA-F could directly suppress the functional activity of immune T cells not only to transfer CS, but also to deliver help to B cells in an in vitro PFC response. This suppressive complex is antigen-nonspecific and does not require Ly2+ T cells in the assay population for suppressive activity. These results indicate that effector factors of the suppressor circuit require two molecules; one that contains the functional suppressor material and one that serves as a "schlepper," a molecule needed to deliver the suppression to the appropriate target cell. The ability to construct a functional suppressor complex from two subfactors raised against different antigens, using different immunization procedures, which were isolated from factors exhibiting different functional activities suggests that certain cells of the immune system may play a universal role in "transducing" the suppressive signal.

scholarly journals Regulation of immune responses by I-J gene products. I. Production and characterization of anti-I-J monoclonal antibodies.

1981 ◽  
Vol 154 (5) ◽  
pp. 1570-1583 ◽  
Author(s):  
C Waltenbaugh
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Immune Responses ◽  
Biochemical Characterization ◽  
Antigenic Determinants ◽  
Functional Screening ◽  
Gene Products ◽  
Suppressor Factor

Using a novel, two-step functional screening procedure, we have isolated hybridoma B cell lines secreting monoclonal antibodies directed against gene products of the I-Jb and I-Jk subregions of the mouse H-2 complex. These monoclonal antibodies act in vitro by allowing nonresponder spleen cells to respond to normally suppressive quantities of poly(Glu50Tyr50) (GT) (WF8 series of anti-I-Jk monoclonal antibodies) or to suboptimal concentration of poly(Glu60Ala30Tyr10) (WF9 series of anti-I-Jb monoclonal antibodies). Some of the culture supernates that show augmenting activity bind GT-specific T cell-derived suppressor factor (GT-TsF), indicating that some monoclonal antiantibodies display a nonspecific enhancing effect, or, more likely, that anti-I-J monoclonal antibodies have been produced against I-J determinants not found on TsF. It is this last possibility that is most intriguing and that might serve as a means for exploring the heterogeneity of the I-J subregion. It is also possible that some of our monoclonal anti-I-J antibodies might detect antigenic determinants selectively expressed on suppressor T cells, helper T cells, and/or macrophages. In addition, we have demonstrated that monoclonal anti-I-J antibodies should be useful in the biochemical characterization and purification of a monoclonal GT-TsF. These haplotype-specific anti-I-J monoclonal antibodies should prove to be powerful tools for future studies exploring the role of I-J gene products in the regulation of specific immune responses.

scholarly journals Genetic control of immune responses in vitro. VI. Experimental conditions for the development of helper T-cell activity specific for the terpolymer L-glutamic aicd60-L-alanine30-L-tyrosine10 (GAT) in nonresponder mice.

1975 ◽  
Vol 142 (1) ◽  
pp. 50-60 ◽  
Author(s):  
J A Kapp ◽  
C W Pierce ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Bovine Serum Albumin ◽  
Immune Responses ◽  
Specific Antibody ◽  
Cell Activity ◽  
Antibody Responses ◽  
Helper T Cells ◽  
Experimental Conditions

Mice which are genetic nonresponders to the random terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) not only fail to develop GAT-specific antibody responses when stimulated with soluble GAT either in vivo or in vitro, but develop GAT-specific T cells which suppress the GAT-specific plaque-forming cell response of normal nonresponder mice stimulated with GAT complexed to methylated bovine serum albumin (MBSA).Thus, both responder and nonresponder mice have T cells which recognize GAT. However, nonresponder mice can develop GAT-specific helper T cells if immunized with GAT bound to MBSA or to macrophages. The relevance of Ir gene-controlled responses is discussed.

scholarly journals Immunostimulatory Effect of Zanthoxylum schinifolium-Based Complex Oil Prepared by Supercritical Fluid Extraction in Splenocytes and Cyclophosphamide-Induced Immunosuppressed Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hak Yong Lee ◽  
Young Mi Park ◽  
Yang Hee Lee ◽  
Yang Gyu Kang ◽  
Hyang Man Lee ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Nk Cell ◽  
Cell Activity ◽  
Pharmacological Activities ◽  
Inflammatory Cytokine Production ◽  
Immunostimulatory Effect ◽  
Zanthoxylum Schinifolium

Complex oil of Zanthoxylum schinifolium and Perilla frutescens seed (ZPCO) is used as a traditional medicine due to its pharmacological activities. The aim of this study was to investigate the immunostimulatory effect of ZPCO in isolated splenocytes as well as in an immunosuppressed rat model, which was generated via oral administration of cyclophosphamide. Notably, our results showed that ZPCO exerted an immunity-enhancing effect both in vitro and in vivo. Specifically, ZPCO treatment enhanced the viability and inflammatory cytokine production of splenocytes and NK cell activity in vitro. Moreover, this product improved host defense under immunosuppressive conditions by increasing the number of immune cells and promoting the expression of cytokines involved in immune responses. Our results suggest that complex oil including Z. schinifolium should be explored as a novel immunostimulatory agent that could potentially be used for therapeutic purposes or as an ingredient in functional foods.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. V. H-2 homology requirements for the production of a minor locus-induced suppressor factor.

1977 ◽  
Vol 146 (4) ◽  
pp. 1152-1157 ◽  
Author(s):  
D L Kastner ◽  
R R Rich ◽  
L Chu ◽  
S S Rich
Keyword(s):  
Major Histocompatibility Complex ◽  
Immune Responses ◽  
Regulatory Mechanisms ◽  
Mixed Leukocyte Reaction ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Histocompatibility Complex ◽  
A Minor

A mixed leukocyte reaction suppressor factor is produced by spleen cells sensitized in vivo and restimulated in vitro across non-H-2 antigenic barriers. Cells capable of producing this factor appear in the spleens of minor locus-immunized animals later than in animals sensitized to major histocompatibility complex-encoded antigens. However, both H-2 and non H-2-induced factors suppress proliferative responses to any alloantigen. Splenocytes from animals immunized with H-2-identical, minor locus-disparate cells produce suppressor factor in vitro only when restimulated with cells sharing both H-2 and non-H-2 antigens with the in vivo stimulators.

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