scholarly journals Regulatory T Cells as an Escape Mechanism to the Immune Response in Taenia crassiceps Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Laura Adalid-Peralta ◽  
Alexander Lopez-Roblero ◽  
Cynthia Camacho-Vázquez ◽  
Marisol Nájera-Ocampo ◽  
Adrián Guevara-Salinas ◽  
...  
Keyword(s):  
Post Infection ◽  
Proliferative Response ◽  
T Regulatory Cells ◽  
Mouse Strains ◽  
Cell Contact ◽  
Susceptible Mouse ◽  
Taenia Crassiceps ◽  
Effector Cells ◽  
Susceptibility To Infection

Murine cysticercosis by Taenia crassiceps is a model for human neurocysticercosis. Genetic and/or immune differences may underlie the higher susceptibility to infection in BALB/cAnN with respect to C57BL/6 mice. T regulatory cells (Tregs) could mediate the escape of T. crassiceps from the host immunity. This study is aimed to investigate the role of Tregs in T. crassiceps establishment in susceptible and non-susceptible mouse strains. Treg and effector cells were quantified in lymphoid organs before infection and 5, 30, 90, and 130 days post-infection. The proliferative response post-infection was characterized in vitro. The expression of regulatory and inflammatory molecules was assessed on days 5 and 30 post-infection. Depletion assays were performed to assess Treg functionality. Significantly higher Treg percentages were observed in BALB/cAnN mice, while increased percentages of activated CD127+ cells were found in C57BL/6 mice. The proliferative response was suppressed in susceptible mice, and Treg proliferation occurred only in susceptible mice. Treg-mediated suppression mechanisms may include IL-10 and TGFβ secretion, granzyme- and perforin-mediated cytolysis, metabolic disruption, and cell-to-cell contact. Tregs are functional in BALB/cAnN mice. Therefore Tregs could be allowing parasite establishment and survival in susceptible mice but could play a homeostatic role in non-susceptible strains.

scholarly journals Leishmania (Viannia) panamensis - induced cutaneous leishmaniasis in susceptible and resistant mouse strains

1995 ◽  
Vol 37 (6) ◽  
pp. 475-481 ◽  
Author(s):  
H. Goto ◽  
J. I. Rojas ◽  
L. Sporrong ◽  
P. de Carreira ◽  
C. Sánchez ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Post Infection ◽  
Proliferative Response ◽  
Cellular Response ◽  
Initial Response ◽  
Mouse Strains ◽  
Resistant Mouse ◽  
Inoculation Site ◽  
Lymph Node Cells ◽  
Foot Pad

We studied the susceptibility to Leishmania (Viannia) panamensis in strains of mice. The C57BL/6 strain was resistant and showed self-controlled lesion at the injected foot pad. The BALB/c and DBA/2J strains were susceptible and showed a foot swelling that started day 20 post-infection and progressed to a tumour-like lesion in later period of observation. The CBA/HJ strain was found to be of intermediary resistance. In contrast to other known cutaneous leishmaniasis in mice, the lesion in L. (V.) panamensis-infected mice was restricted to the inoculation site in the skin. In addition, we studied the development of cellular response and antibodies against Leishmania antigen in BALB/c and C57BL/6 strains. The proliferative response of lymph node cells against L. (V.) panamensis antigen was biphasic in both strains. An initial response was seen on day 20, followed by a refractory period between 40 and 80 days and a second response around fourth month post-infection. The response in the latter period was higher in C57BL/6 strain than in BALB/c strain. BALB/c strain presented much higher anti-Leishmania antibody level than C57BL/6 strain. The model and the correlation of immunological variables and the course of the infection are discussed.

scholarly journals Incidence and severity of G6PI-induced arthritis are not increased in genetically distinct mouse strains upon aging

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Nico Andreas ◽  
Sylvia Müller ◽  
Nicole Templin ◽  
Paul M. Jordan ◽  
Harald Schuhwerk ◽  
...  
Keyword(s):  
Immune Cell ◽  
Ex Vivo ◽  
Wild Type Mouse ◽  
Mouse Strains ◽  
Functional Difference ◽  
Susceptible Mouse ◽  
Age Related ◽  
Th Cell ◽  
Old Mice

Abstract Background The incidence of rheumatoid arthritis is correlated with age. In this study, we analyzed the association of the incidence and severity of glucose-6-phosphate isomerase (G6PI)-induced arthritis with age in two different mouse strains. Methods Young and very old mice from two different arthritis-susceptible wild-type mouse strains were analyzed after a single subcutaneous injection of G6PI s.c. The metabolism and the function of synoviocytes were analyzed in vitro, the production of bioactive lipid mediators by myeloid cells and synoviocytes was assessed in vitro and ex vivo by UPLC-MS-MS, and flow cytometry was used to verify age-related changes of immune cell composition and function. Results While the severity of arthritis was independent from age, the onset was delayed in old mice. Old mice showed common signs of immune aging like thymic atrophy associated with decreased CD4+ effector T cell numbers. Despite its decrease, the effector T helper (Th) cell compartment in old mice was reactive and functionally intact, and their Tregs exhibited unaltered suppressive capacities. In homeostasis, macrophages and synoviocytes from old mice produced higher amounts of pro-inflammatory cyclooxygenase (COX)-derived products. However, this functional difference did not remain upon challenge in vitro nor upon arthritis reactions ex vivo. Conclusion While old mice show a higher baseline of inflammatory functions, this does not result in increased reaction towards self-antigens in arthritis-susceptible mouse strains. Together, our data from two different mouse strains show that the susceptibility for G6PI-induced arthritis is not age-dependent.

scholarly journals Adenoviral Delivery of Interleukin-10 Fails To Attenuate Experimental Lyme Disease

2008 ◽  
Vol 76 (12) ◽  
pp. 5500-5507 ◽  
Author(s):  
Charles R. Brown ◽  
Annie Y.-C. Lai ◽  
Steven T. Callen ◽  
Victoria A. Blaho ◽  
Jennifer M. Hughes ◽  
...  
Keyword(s):  
Interleukin 10 ◽  
Lyme Arthritis ◽  
Mouse Strains ◽  
Susceptible Mouse ◽  
Lyme Carditis ◽  
Adenoviral Delivery ◽  
Severity Scores ◽  
C3h Mice

ABSTRACT Production of interleukin-10 (IL-10) by C57BL/6 mice following infection with Borrelia burgdorferi has been proposed as a mechanism whereby resistance to the development of experimental Lyme arthritis is maintained. In the current study, we sought to determine the role of IL-10 during infection of arthritis- and carditis-susceptible C3H mice. Infection of C3H IL-10−/− mice led to increased joint swelling and arthritis severity scores over those of wild-type C3H mice. Measurement of B. burgdorferi numbers in joints or disseminated tissues indicated a more efficient clearance of spirochetes in the absence of IL-10, similar to that reported in C57BL/6 IL-10−/− mice. However, in contrast to previous in vitro work, infection of C3H IL-10−/− mice led to decreased in vivo expression of the cytokines KC, IL-1β, IL-4, and IL-12p70 in the infected joints. Finally, adenoviral expression of IL-10 in the infected joints of C3H mice was unable to modulate the development of severe Lyme arthritis and had no effect on spirochete clearance or Borrelia-specific antibody production. Development of Lyme carditis appeared to be independent of modulation by IL-10. These results suggest that IL-10 limits the development of joint inflammation in both arthritis-resistant and -susceptible mouse strains infected with B. burgdorferi and that increased IL-10 production cannot rescue genetic susceptibility to development of pathology in this model.

scholarly journals Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

1978 ◽  
Vol 147 (5) ◽  
pp. 1435-1448 ◽  
Author(s):  
U Botzenhardt ◽  
J Klein ◽  
M Ziff
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell System ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Major Histocompatibility ◽  
Effector Cells ◽  
Histocompatibility Complex ◽  
2D Strain

T-cell cytotoxicity of NZV mice was tested after in vitro sensitization against a group of H-2 identical strains (BALB/c, B10.D2, DBA/2, HW19). A highly significant and unexpected unidirectional cell-mediated lympholysis (CML) reaction by the sensitized NZB effector cells on these targets was found. After sensitization in vitro with stimulator cells of one H-2d strain, NZB effector cells (H-2d) lysed all other H-2d targets and to a lesser degree, some non-H-2d targets (C57BL/10, DBA/1, B10.Q, CBA, B10.S, A.SW). NZB targets were not lysed. Differences in the major histocompatibility region between NZB and other H-2d strains could be excluded as a possible explanation for the observed reaction of NZB (H-2d) against other H-2d strains. These results consequently represent the first description of a primary in vitro CML directed against determinants not coded for in the major histocompatibility complex. The responsible effector cells are demonstrated to be T cells. The CML of NZB against H-2 identiical targets appears best explained by a reaction against minor histocompatibility antigens. This, and the observed cross-reactions, would indicate that the cytotoxic T-cell system in NZB mice is not subjected to restrictions found in all normal mouse strains tested until now under similar conditions. It is suggested that this hyperreactivity is related to the autoimmune responsiveness of the NZB strain.

scholarly journals Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex.

1975 ◽  
Vol 141 (6) ◽  
pp. 1348-1364 ◽  
Author(s):  
G M Shearer ◽  
T G Rehn ◽  
C A Garbarino
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Resistant Mouse ◽  
Effector Cells ◽  
Histocompatibility Complex

Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined. The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis. Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis. Homology at the K serological region or at K plus I-A in the B10.A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10.D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis. Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions. Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP-modified autologous cytotoxic system. These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components.

scholarly journals GENETIC CONTROL OF CELL-MEDIATED LYMPHOLYSIS IN MOUSE

1974 ◽  
Vol 140 (6) ◽  
pp. 1534-1546 ◽  
Author(s):  
Dolores J. Schendel ◽  
Fritz H. Bach
Keyword(s):  
Genetic Control ◽  
Congenic Mouse ◽  
Mouse Strains ◽  
Effector Cells ◽  
Congenic Mouse Strains ◽  
Cytotoxic Effector

H-2 congenic mouse strains were tested in vitro to investigate the genetic control of cell-mediated lympholysis (CML). Combinations were selected such that differences in various segments of H-2 could be examined for their ability to stimulate production of effector cells and to serve as targets for lysis. Particular emphasis was directed towards understanding the roles of LD and SD. SD-region differences are important in the sensitization of effector cells and they also function as strong targets for lysis, or as markers for the CML targets. LD differences are also important for sensitization of cytotoxic effector cells, but they serve only as very weak targets for lysis. Collaboration occurs between LD and SD in generation of CML. The nature of this interaction can be of two types: together LD and SD can produce CML which neither difference alone can stimulate; LD can enhance a CML response stimulated by SD-region differences alone.

scholarly journals Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model

2011 ◽  
Vol 209 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Ikuko Ueki ◽  
Norio Abiru ◽  
Kentaro Kawagoe ◽  
Yuji Nagayama
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Recombinant Adenovirus ◽  
Interleukin 10 ◽  
T Cell Response ◽  
Tsh Receptor ◽  
Mouse Strains ◽  
Susceptible Mouse ◽  
Ifn Γ

Experimental Graves'-like hyperthyroidism can be induced in susceptible mouse strains by repetitive immunizations with recombinant adenovirus expressing the human full-length TSH receptor (TSHR) or its A-subunit. Previous studies have shown that splenocytes from immunized mice produce interferon (IFN)-γ and interleukin (IL) 10 in response to antigen stimulation in an in vitro T cell recall assay. Although IFN-γ is now well known to be essential for disease induction, the role(s) played by IL10 are unknown. Therefore, this study was conducted to clarify the significance of endogenous IL10 in the pathogenesis of experimental Graves' disease using IL10 deficient (IL10−/−) mice. Our results show that T cell response was augmented when estimated by their antigen-specific secretion of the key cytokine IFN-γ, but B cell function was dampened, that is, anti-TSHR antibody titers were decreased in IL10−/− mice, resulting in a lower incidence of Graves' hyperthyroidism (54% in IL10+/+ vs 25% in IL10−/−). Thus, in addition to IFN-γ, these data clarified the role of IL10 for optimizing anti-TSHR antibody induction and eliciting Graves' hyperthyroidism in our Graves' mouse model.

scholarly journals Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Nina Pilat ◽  
Christoph Klaus ◽  
Karin Hock ◽  
Ulrike Baranyi ◽  
Lukas Unger ◽  
...  
Keyword(s):  
Clinical Setting ◽  
Large Scale ◽  
T Regulatory Cells ◽  
Third Party ◽  
Mixed Chimerism ◽  
Effector Cells ◽  
Treg Population ◽  
Donor Specific Tolerance ◽  
Specific Tolerance

Induction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM) transplantation (BMT) model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4+CD25+in vitroactivated nTregs are superior to TGFβinduced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs) led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5×106cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting.

scholarly journals Increased Expression of TLR4 in Circulating CD4+T Cells in Patients with Allergic Conjunctivitis and In Vitro Attenuation of Th2 Inflammatory Response by Alpha-MSH

2020 ◽  
Vol 21 (21) ◽  
pp. 7861 ◽  
Author(s):  
Jane E. Nieto ◽  
Israel Casanova ◽  
Juan Carlos Serna-Ojeda ◽  
Enrique O. Graue-Hernández ◽  
Guillermo Quintana ◽  
...  
Keyword(s):  
Allergic Conjunctivitis ◽  
T Regulatory Cells ◽  
Mononuclear Cells ◽  
Cell Subset ◽  
Allergic Diseases ◽  
Peripheral Blood Mononuclear ◽  
Effector Cells ◽  
Inflammatory Microenvironment ◽  
Specific Stimulation

Ocular allergic diseases are frequently seen in ophthalmological clinical practice. Immunological damage is mediated by a local Th2 inflammatory microenvironment, accompanied by changes in circulating cell subsets, with more effector cells and fewer T regulatory cells (Tregs). This study aimed to evaluate the involvement of toll-like receptor 4 (TLR4) and α-melanocyte stimulating hormone (α-MSH) in the immune regulation associated with perennial allergic conjunctivitis (PAC). We performed an Ag-specific stimulation during 72 h of culturing with or without lipopolysaccharide (LPS) or α-MSH in peripheral blood mononuclear cells (PBMC), analyzing the cell subsets and cytokines induced by the stimuli. We also determined α-MSH in tear samples from healthy donors (HD) or PAC patients. Our findings demonstrate an immunological dysregulation characterized by an increased frequency of CD4+TLR4+ in the PBMC of patients with PAC, compared to HD. Most of these CD4+TLR4+ cells were also CD25+, and when α-MSH was added to the culture, the percentage of CD4+CD25+FoxP3+ increased significantly, while the percentage of CD69+ cells and cytokines IL-4 and IL-6 were significantly decreased. In tears, we found an increased concentration of α-MSH in PAC patients, compared with HD. These findings indicate a novel mechanism involved in controlling ocular allergic diseases, in which α-MSH diminishes the concentration of IL-6 and IL-4, restoring the frequency of Tregs and down-regulating CD4 activation. Moreover, we demonstrated the involvement of CD4+TLR4+ cells as an effector cell subset in ocular allergy.

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