scholarly journals LACK-Specific CD4+ T Cells That Induce Gamma Interferon Production in Patients with Localized Cutaneous Leishmaniasis during an Early Stage of Infection

2002 ◽  
Vol 70 (6) ◽  
pp. 3122-3129 ◽  
Author(s):  
Eliane Bourreau ◽  
Ghislaine Prévot ◽  
Jacques Gardon ◽  
Roger Pradinaud ◽  
Hitoshi Hasagewa ◽  
...  
Keyword(s):  
T Cells ◽  
Early Stage ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Effector Memory ◽  
Cellular Source ◽  
Effector Memory Cells ◽  
Ifn Γ

ABSTRACT The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a candidate vaccine against leishmaniasis, and the cellular source of the cytokines produced in response to these antigens were analyzed in patients infected with Leishmania guyanensis. Gamma interferon (IFN-γ) and interleukin-10 (IL-10) were produced in response to LACK. Although LACK-specific CD4+ cells producing IFN-γ were isolated only during the early phase of infection (less than 30 days following the onset of infection), cells producing IL-10 in response to LACK were detected in all patients. CD4+ T cells producing IFN-γ and IL-13 were produced in response to SLA in all patients. SLA- and LACK-specific T cells are effector memory cells, as they are CD45RA− CCR7− CD4+ T cells. CD4+ T cells producing IFN-γ are CD62L−, and CD4+ T cells producing IL-10 are CD62L+, indicating that these cells have different tissue-homing capacities. These findings show that SLA and LACK induce both type 1 (IFN-γ) and type 2 (IL-10 or IL-13) cell responses.

scholarly journals Populations of Human T Lymphocytes That Traverse the Vascular Endothelium Stimulated by Borrelia burgdorferi Are Enriched with Cells That Secrete Gamma Interferon

2004 ◽  
Vol 72 (3) ◽  
pp. 1530-1536 ◽  
Author(s):  
Edna I. Gergel ◽  
Martha B. Furie
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Vascular Endothelium ◽  
Human Peripheral Blood ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Ifn Γ

ABSTRACT Some diseases are characterized by prevalence in the affected tissues of type 1 T lymphocytes, which secrete gamma interferon (IFN-γ) and other proinflammatory cytokines. For example, type 1 T cells predominate in the lesions of patients with Lyme disease, which is caused by the bacterium Borrelia burgdorferi. We used an in vitro model of the blood vessel wall to test the premise that the vascular endothelium actively recruits circulating type 1 T cells to such lesions. When T lymphocytes isolated from human peripheral blood were examined, the populations that traversed monolayers of resting human umbilical vein endothelial cells (HUVEC) or HUVEC stimulated by interleukin-1β or B. burgdorferi were markedly enriched for T cells that produced IFN-γ compared to the initially added population of T cells. No enrichment was seen for cells that produced interleukin-4, a marker for type 2 T lymphocytes. Very late antigen-4 and CD11/CD18 integrins mediated passage of the T cells across both resting and stimulated HUVEC, and the endothelium-derived chemokine CCL2 (monocyte chemoattractant protein 1) was responsible for the enhanced migration of T cells across stimulated HUVEC. These results suggest that the vascular endothelium may contribute to the selective accumulation of type 1 T cells in certain pathological lesions, including those of Lyme disease.

scholarly journals Interdependency of Interleukin-10 and Interleukin-12 in Regulation of T-Cell Differentiation and Effector Function of Monocytes in Response to Stimulation withCryptococcus neoformans

2001 ◽  
Vol 69 (10) ◽  
pp. 6064-6073 ◽  
Author(s):  
Cinzia Retini ◽  
Thomas R. Kozel ◽  
Donatella Pietrella ◽  
Claudia Monari ◽  
Francesco Bistoni ◽  
...  
Keyword(s):  
T Cells ◽  
Critical Role ◽  
Principal Component ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
T Helper ◽  
Ifn Γ ◽  
Capsular Material ◽  
Type Response

ABSTRACT We previously demonstrated that the principal component of capsular material of Cryptococcus neoformans, glucuronoxylomannan (GXM), induces interleukin-10 (IL-10) secretion from human monocytes. Here we report that encapsulation of the yeast with GXM is able to down-regulate interleukin-12 (IL-12) production by monocytes that would normally occur in the absence of encapsulation. This phenomenon appeared to be the result of inhibition of the phagocytic process by encapsulation with GXM as well as of negative signals such as IL-10 secretion produced by interaction of GXM with leukocytes. Decreased secretion of IL-12 correlated with decreased release of gamma interferon (IFN-γ) from T cells, suggesting a role for encapsulation with GXM in hindering a T helper type 1 (Th1) response. This is supported by the ability of encapsulation with GXM to limit increased expression of B7-1 costimulatory molecules that otherwise might limit IL-10 secretion. Endogenous IL-10 played a critical role in modulatory activity associated with encapsulation with GXM. Blocking IL-10 with monoclonal antibody to IL-10 resulted in increased (i) IL-12 secretion, (ii) IFN-γ release from T cells, and (iii) killing of C. neoformans by monocytes. These results suggest that encapsulation with GXM limits development of a protective Th1-type response, an inhibitory process in which IL-10 plays a critical role. Scavengers of GXM and/or IL-10 could be useful in a protective Th1-type response in patients with cryptococcosis.

scholarly journals Interleukin-10 Has Different Effects on Proliferation of Listeria monocytogenes in Livers and Spleens of Mice

2000 ◽  
Vol 68 (8) ◽  
pp. 4666-4672 ◽  
Author(s):  
Janneke N. Samsom ◽  
Akke Annema ◽  
Minke F. Geertsma ◽  
Jan A. M. Langermans ◽  
Paul H. P. Groeneveld ◽  
...  
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
Primary Infection ◽  
Secondary Infection ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Number Of Bacteria

ABSTRACT The aim of this study was to investigate the effect of interleukin-10 (IL-10) on the course of Listeria monocytogenes infection in naive and immune mice. Treatment with IL-10 during the course of a primary infection significantly decreased the number of bacteria in the spleen and did not affect the number in the liver. During a secondary infection in immune mice treated with IL-10, the number of bacteria was significantly lower in the spleen but significantly higher in the liver in comparison to mock-treated immune mice. IL-10 treatment during a primary Listeria infection decreased the concentration of gamma interferon (IFN-γ) in plasma and the toxoplasmastatic activity of macrophages, whereas it increased the percentage of mildly CD3-positive T cells in the spleen. During a secondary infection, the concentration of IFN-γ in plasma was decreased on day 1 but remained unaffected during later days of infection. From these results, we conclude that IL-10 has different effects on the proliferation of L. monocytogenes in the spleen and liver during primary and secondary Listeriainfections.

scholarly journals Vaccinated C57BL/6 Mice Develop Protective and Memory T Cell Responses to Coccidioides posadasii Infection in the Absence of Interleukin-10

2013 ◽  
Vol 82 (2) ◽  
pp. 903-913 ◽  
Author(s):  
Chiung-Yu Hung ◽  
Natalia Castro-Lopez ◽  
Garry T. Cole
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
Interleukin 10 ◽  
Effector Memory ◽  
Wild Type ◽  
Coccidioides Posadasii ◽  
Content Type ◽  
Cell Immunity ◽  
Ifn Γ

ABSTRACTHigh concentrations of lung tissue-associated interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine, correlate with susceptibility of mice toCoccidioidesspp. infection. In this study, we found that macrophages, dendritic cells, neutrophils, and both CD8+and CD4+T cells recruited toCoccidioides posadasii-infected lungs of nonvaccinated and vaccinated mice contributed to the production of IL-10. The major IL-10-producing leukocytes were CD8+T cells, neutrophils, and macrophages in lungs of nonvaccinated mice, while both Foxp3+and Foxp3−subsets of IL-10+CD4+T cells were significantly elevated in vaccinated mice. Profiles of the recruited leukocytes in lungs revealed that only CD4+T cells were significantly increased inIL-10−/−knockout mice compared to their wild-type counterparts. Furthermore,ex vivorecall assays showed that CD4+T cells isolated from vaccinatedIL-10−/−mice compared to vaccinated wild-type mice produced significantly higher amounts of IL-2, gamma interferon (IFN-γ), IL-4, IL-6, and IL-17A in the presence of a coccidioidal antigen, indicating that IL-10 suppresses Th1, Th2, and Th17 immunity toCoccidioidesinfection. Analysis of absolute numbers of CD44+CD62L−CD4+T effector memory T cells (TEM) and IFN-γ- and IL-17A-producing CD4+T cells in the lungs ofCoccidioides-infected mice correlated with better fungal clearance in nonvaccinatedIL-10−/−mice than in nonvaccinated wild-type mice. Our results suggest that IL-10 suppresses CD4+T-cell immunity in nonvaccinated mice duringCoccidioidesinfection but does not impede the development of a memory response nor exacerbate immunopathology of vaccinated mice over at least a 4-month period after the last immunization.

scholarly journals Dysregulated Synthesis of Intracellular Type 1 and Type 2 Cytokines by T Cells of Patients with Cutaneous T-Cell Lymphoma

1999 ◽  
Vol 6 (1) ◽  
pp. 79-84 ◽  
Author(s):  
Bang-Ning Lee ◽  
Madeleine Duvic ◽  
Chih-Kwang Tang ◽  
Carlos Bueso-Ramos ◽  
Zeev Estrov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Study Groups ◽  
Cutaneous T Cell Lymphoma ◽  
Healthy Donors ◽  
Type 2 Cytokines ◽  
Ifn Γ

ABSTRACT Mycosis fungoides (MF) and Sezary syndrome (SS) are the two main clinical entities of cutaneous T-cell lymphoma (CTCL). As the disease progresses from MF to SS, a switch from a type 1 (interleukin [IL]-2 and gamma interferon [IFN-γ]) to a type 2 (IL-4) cytokine production profile occurs. Although roles for type 1 and type 2 cytokines in the pathogenesis of CTCL have been proposed, the cellular origins of these cytokines are unclear. Using flow cytometry to identify individual T-cell subsets, we studied cytokine synthesis by the T cells of 13 patients with SS and 12 with MF and 9 hematologically healthy donors. Upon activation with phorbol 12-myristate 13-acetate (PMA), the numbers of T cells synthesizing IL-2 were similar for all study groups. Whereas the predominant T-cell producing IL-2 in healthy donors and in those with MF was CD7+, in patients with SS, it was CD7−. Although the number of IL-4+CD4+ T cells was low for all study groups, there was a significantly higher number of IL-4+ CD8+ T cells in patients with MF than in those with SS or healthy donors. There was a decline in the number of IFN-γ-producing T cells in CTCL donors compared to that in healthy donors. More importantly, there was a significant decrease in the number of IFN-γ-producing T cells with disease progression from MF to SS. The inability of these T cells to synthesize IFN-γ may have prognostic value in CTCL, since it may be responsible for the progression of the disease from MF to SS.

scholarly journals Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases.

1996 ◽  
Vol 9 (4) ◽  
pp. 532-562 ◽  
Author(s):  
D R Lucey ◽  
M Clerici ◽  
G M Shearer
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Gamma Interferon ◽  
Human Diseases ◽  
Delayed Type Hypersensitivity ◽  
Type 2 Cytokines ◽  
Th1 And Th2

In the mid-1980s, Mosmann, Coffman, and their colleagues discovered that murine CD4+ helper T-cell clones could be distinguished by the cytokines they synthesized. The isolation of human Th1 and Th2 clones by Romagnani and coworkers in the early 1990s has led to a large number of reports on the effects of Th1 and Th2 on the human immune system. More recently, cells other than CD4+ T cells, including CD8+ T cells, monocytes, NK cells, B cells, eosinophils, mast cells, basophils, and other cells, have been shown to be capable of producing "Th1" and "Th2" cytokines. In this review, we examine the literature on human diseases, using the nomenclature of type 1 (Th1-like) and type 2 (Th2-like) cytokines, which includes all cell types producing these cytokines rather than only CD4+ T cells. Type 1 cytokines include interleukin-2 (IL-2), gamma interferon, IL-12 and tumor necrosis factor beta, while type 2 cytokines include IL-4, IL-5, IL-6, IL-10, and IL-13. In general, type 1 cytokines favor the development of a strong cellular immune response whereas type 2 cytokines favor a strong humoral immune response. Some of these type 1 and type 2 cytokines are cross-regulatory. For example, gamma interferon and IL-12 decrease the levels of type 2 cytokines whereas IL-4 and IL-10 decrease the levels of type 1 cytokines. We use this cytokine perspective to examine human diseases including infections due to viruses, bacteria, parasites, and fungi, as well as selected neoplastic, atopic, rheumatologic, autoimmune, and idiopathic-inflammatory conditions. Clinically, type 1 cytokine-predominant responses should be suspected in any delayed-type hypersensitivity-like granulomatous reactions and in infections with intracellular pathogens, whereas conditions involving hypergammaglobulinemia, increased immunoglobulin E levels, and/or eosinophilia are suggestive of type 2 cytokine-predominant conditions. If this immunologic concept is relevant to human diseases, the potential exists for novel cytokine-based therapies and novel cytokine-directed preventive vaccines for such diseases.

scholarly journals Essential Roles for CD8+ T Cells and Gamma Interferon in Protection of Mice against Retrovirus-Induced Immunosuppression

2002 ◽  
Vol 76 (1) ◽  
pp. 450-454 ◽  
Author(s):  
Ulf Dittmer ◽  
Brent Race ◽  
Karin E. Peterson ◽  
Ingunn M. Stromnes ◽  
Ronald J. Messer ◽  
...  
Keyword(s):  
T Cells ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Antibody Responses ◽  
Mhc I ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
Immunosuppressive Cytokine ◽  
Ifn Γ

ABSTRACT It is known that both animal and human retroviruses typically cause immunosuppression in their respective hosts, but the mechanisms by which this occurs are poorly understood. The present study uses Friend virus (FV) infections of mice as a model to determine how major histocompatibility complex (MHC) genes influence immunosuppression. Previously, MHC-I genes were shown to influence antibody responses to potent antigenic challenges given during acute FV infection. The mapping of an immune response to an MHC-I gene implicated CD8+ T cells in the mechanism, so we directly tested for their role by using in vivo CD8+ T-cell depletions. Mice resistant to FV-induced immunosuppression became susceptible when they were depleted of CD8+ T cells. Resistance also required gamma interferon (IFN-γ), as in vivo neutralization of IFN-γ converted mice from a resistant to susceptible phenotype. On the other hand, susceptibility to FV-induced immunosuppression was dependent on the immunosuppressive cytokine, interleukin-10 (IL-10), as antibody responses were restored in susceptible mice when IL-10 function was blocked in vivo. Thus, FV-induced immunosuppression of antibody responses involves complex mechanisms controlled at least in part by CD8+ T cells.

Exercise-induced change in type 1 cytokine-producing CD8+ T cells is related to a decrease in memory T cells

2002 ◽  
Vol 93 (2) ◽  
pp. 645-648 ◽  
Author(s):  
Tobias Ibfelt ◽  
Emil Wolsk Petersen ◽  
Helle Bruunsgaard ◽  
Marie Sandmand ◽  
Bente Klarlund Pedersen
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Treadmill Running ◽  
Intracellular Expression ◽  
Ifn Γ ◽  
Exercise Induced ◽  
Response To Exercise ◽  
Type 1 Cytokine

In response to exercise, both CD4+ and CD8+ T cells are mobilized to the blood, but the levels of these cells decline below preexercise values in the postexercise period. T cells are functionally polarized, depending on the cytokines they produce. Type 1 cells produce, e.g., interferon (INF)-γ, whereas type 2 produce, e.g., interleukin (IL)-4. It was recently demonstrated that exercise induces a decrease in the percentage of type 1 T cells. The present study further investigated the mechanisms underlying the exercise-induced shift in the balance between type 1 and type 2 cytokine-producing cells. Seven healthy men performed 1.5 h of treadmill running with blood samples drawn before exercise, at the end of exercise, and 2 h after exercise. Intracellular expression of IFN-γ, IL-2, and IL-4 was detected in CD4+ and CD8+ T cells after stimulation with phorbol 12-myristate 13-acetate and ionomycin. Intracellular expression of IFN-γ within CD8+ cells was decreased in the postexercise period compared with values obtained immediately after exercise, whereas the expression of IL-2 and IL-4 did not change within the CD4+and CD8+ cell populations. The decrease in IFN-γ-producing CD8+ T cells postexercise was negatively correlated with a decrease in percentage of memory T cells within the CD8+ cells ( r = −0.94; P≤ 0.002). In conclusion, this study demonstrates that the exercise-induced change in type 1 cytokine-producing T cells is related to a decline in memory cells.

scholarly journals Involvement of T Cells in Enhanced Resistance to Klebsiella pneumoniae Septicemia in Mice Treated with Liposome-Encapsulated Muramyl Tripeptide Phosphatidylethanolamine or Gamma Interferon

1998 ◽  
Vol 66 (5) ◽  
pp. 1962-1967 ◽  
Author(s):  
Timo L. M. ten Hagen ◽  
Wim van Vianen ◽  
Huub F. J. Savelkoul ◽  
Hubertine Heremans ◽  
Wim A. Buurman ◽  
...  
Keyword(s):  
T Cells ◽  
Klebsiella Pneumoniae ◽  
Host Defense ◽  
Cell Activation ◽  
Nk Cell ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Th1 Cell ◽  
Cd8 Cells ◽  
Ifn Γ

ABSTRACT We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-γ) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-γ. Depletion of circulating IFN-γ resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-γ favors Th1 and NK cell activation.

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