scholarly journals In vivo role of IFN-γ produced by antigen-presenting cells in early host defense against intracellular pathogens

2003 ◽  
Vol 33 (10) ◽  
pp. 2666-2675 ◽  
Author(s):  
Kazutomo Suzue ◽  
Takashi Asai ◽  
Tsutomu Takeuchi ◽  
Shigeo Koyasu
Keyword(s):  
Host Defense ◽  
Antigen Presenting Cells ◽  
Intracellular Pathogens ◽  
Ifn Γ ◽  
Antigen Presenting

scholarly journals Selective Abrogation of Major Histocompatibility Complex Class II Expression on Extrahematopoietic Cells in Mice Lacking Promoter IV of the Class II Transactivator Gene

2001 ◽  
Vol 194 (4) ◽  
pp. 393-406 ◽  
Author(s):  
Jean-Marc Waldburger ◽  
Tobias Suter ◽  
Adriano Fontana ◽  
Hans Acha-Orbea ◽  
Walter Reith
Keyword(s):  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Thymic Epithelial Cells ◽  
Class Ii Transactivator ◽  
Ifn Γ ◽  
Definition Of ◽  
Antigen Presenting ◽  
Mhcii Expression

MHC class II (MHCII) molecules play a pivotal role in the induction and regulation of immune responses. The transcriptional coactivator class II transactivator (CIITA) controls MHCII expression. The CIITA gene is regulated by three independent promoters (pI, pIII, pIV). We have generated pIV knockout mice. These mice exhibit selective abrogation of interferon (IFN)-γ–induced MHCII expression on a wide variety of non-bone marrow–derived cells, including endothelia, epithelia, astrocytes, and fibroblasts. Constitutive MHCII expression on cortical thymic epithelial cells, and thus positive selection of CD4+ T cells, is also abolished. In contrast, constitutive and inducible MHCII expression is unaffected on professional antigen-presenting cells, including B cells, dendritic cells, and IFN-γ–activated cells of the macrophage lineage. pIV−/− mice have thus allowed precise definition of CIITA pIV usage in vivo. Moreover, they represent a unique animal model for studying the significance and contribution of MHCII-mediated antigen presentation by nonprofessional antigen-presenting cells in health and disease.

The Second Signal in Antigen-Presenting Cells: Complementary JAK1/JAK2 and CD40 Signalling Mediate Pro-Inflammatory Activation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1261-1261
Author(s):  
Michael Conzelmann ◽  
Elena Rodionova ◽  
Michael Hess ◽  
Annika Zota ◽  
Thomas Giese ◽  
...  
Keyword(s):  
Antigen Presenting Cells ◽  
Chronic Inflammatory Disease ◽  
Janus Kinase ◽  
Th2 Cytokines ◽  
Inflammatory Activation ◽  
Cd40 Activation ◽  
Ifn Γ ◽  
Antigen Presenting

Abstract CD40Ligand (CD40L) represents a strong endogenous danger signal associated with chronic inflammatory disease. CD40L induces pro-inflammatory activation of CD40 expressing antigen-presenting cells (APC) such as DCs, monocytes, B-cells and endothelial cells; however, CD40 activation alone is insufficient to induce interleukin (IL)-12p70 secretion. Using quantitative Western blotting and siRNA inhibition of protein expression we demonstrate that cytokine-induced Janus kinase (JAK)1 and/or JAK2 activation mediates a complementary second signal for the production of IL- 12p70, whereas tyrosine kinase (Tyk)2 activation has inhibitory effects. Furthermore, JAK1 activation reciprocally reduced IL-10 production. The mechanism of JAK modulation of CD40 signals in dendritic cells (DCs) involved transcriptional regulation. The Th1 and Th2 cytokines interferon (IFN)-γ and IL-4 both enhance IL-12p70 via activation of the same JAKs. However due to a weaker JAK activity, IL-4 signalling has to persist much longer than IFN-γ signalling in order to induce similar amounts of IL-12p70. This different dependence on signalling persistence may give rise to the distinct biological characteristics of Th1/Th2 cytokines and may explain the pleiotropic in vivo and in vitro effects of IL-4. Complementary CD40 and JAK activity is essential for IL-12p70 secretion by all human APC studied. This strict requirement of two complementary signals opens a new way of interfering with CD40L induced APC activation indirectly by modulating the “second signal” JAK.

Sensitization of Allo-Specific T Lymphocytes in vivo: Role of Antigen-Presenting Cells

Immunobiology ◽  
1992 ◽  
Vol 186 (5) ◽  
pp. 362-377 ◽  
Author(s):  
Mohammad A.A. Ibrahim ◽  
Joanna S. Ibrahim ◽  
Benjamin M. Ibrahim ◽  
David R. Ibrahim
Keyword(s):  
T Lymphocytes ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

scholarly journals Interleukin 12–dependent Interferon γ Production by CD8α+Lymphoid Dendritic Cells

1999 ◽  
Vol 189 (12) ◽  
pp. 1981-1986 ◽  
Author(s):  
Toshiaki Ohteki ◽  
Taro Fukao ◽  
Kazutomo Suzue ◽  
Chikako Maki ◽  
Mamoru Ito ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Nk Cell ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Antigen Presenting

We investigated the role of antigen-presenting cells in early interferon (IFN)-γ production in normal and recombinase activating gene 2–deficient (Rag-2−/−) mice in response to Listeria monocytogenes (LM) infection and interleukin (IL)-12 administration. Levels of serum IFN-γ in Rag-2−/− mice were comparable to those of normal mice upon either LM infection or IL-12 injection. Depletion of natural killer (NK) cells by administration of anti-asialoGM1 antibodies had little effect on IFN-γ levels in the sera of Rag-2−/− mice after LM infection or IL-12 injection. Incubation of splenocytes from NK cell–depleted Rag-2−/− mice with LM resulted in the production of IFN-γ that was completely blocked by addition of anti–IL-12 antibodies. Both dendritic cells (DCs) and monocytes purified from splenocytes were capable of producing IFN-γ when cultured in the presence of IL-12. Intracellular immunofluorescence analysis confirmed the IFN-γ production from DCs. It was further shown that IFN-γ was produced predominantly by CD8α+ lymphoid DCs rather than CD8α− myeloid DCs. Collectively, our data indicated that DCs are potent in producing IFN-γ in response to IL-12 produced by bacterial infection and play an important role in innate immunity and subsequent T helper cell type 1 development in vivo.

Co-localization of class II antigen and exogenous antigen in the rat enterocyte

1993 ◽  
Vol 106 (3) ◽  
pp. 937-940
Author(s):  
P.A. Gonnella ◽  
D.W. Wilmore
Keyword(s):  
Antigen Presenting Cells ◽  
Class Ii ◽  
Major Histocompatibility Antigens ◽  
Exogenous Antigen ◽  
Class Ii Antigen ◽  
Antigen Presenting ◽  
Endocytic Compartments ◽  
Class Ii Antigens

The role of class II major histocompatibility antigens in classical antigen-presenting cells has been described (Unanue (1984) Annu. Rev. Immunol. 2, 395–428; Watts and McConnell (1987) Rev. Immunol. 5, 461–475). Whether enterocytes, which also express class II antigens, can act as antigen-presenting cells in vivo is not known. One pre-requisite for a role for enterocytes in antigen presentation is an interaction between exogenous antigen and class II antigens. Our results demonstrate that class II antigen and exogenous antigen absorbed from the gastrointestinal tract are co-localized within endocytic compartments and along the basolateral membranes of enterocytes.

scholarly journals Recruitment of Antigen-Presenting Cells to the Site of Inoculation and Augmentation of Human Immunodeficiency Virus Type 1 DNA Vaccine Immunogenicity by In Vivo Electroporation

2008 ◽  
Vol 82 (11) ◽  
pp. 5643-5649 ◽  
Author(s):  
Jinyan Liu ◽  
Rune Kjeken ◽  
Iacob Mathiesen ◽  
Dan H. Barouch
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Antigen Presenting Cells ◽  
In Vivo Electroporation ◽  
Immunodeficiency Virus ◽  
Antigen Presenting

ABSTRACT In vivo electroporation (EP) has been shown to augment the immunogenicity of plasmid DNA vaccines, but its mechanism of action has not been fully characterized. In this study, we show that in vivo EP augmented cellular and humoral immune responses to a human immunodeficiency virus type 1 Env DNA vaccine in mice and allowed a 10-fold reduction in vaccine dose. This enhancement was durable for over 6 months, and re-exposure to antigen resulted in anamnestic effector and central memory CD8+ T-lymphocyte responses. Interestingly, in vivo EP also recruited large mixed cellular inflammatory infiltrates to the site of inoculation. These infiltrates contained 45-fold-increased numbers of macrophages and 77-fold-increased numbers of dendritic cells as well as 2- to 6-fold-increased numbers of B and T lymphocytes compared to infiltrates following DNA vaccination alone. These data suggest that recruiting inflammatory cells, including antigen-presenting cells (APCs), to the site of antigen production substantially improves the immunogenicity of DNA vaccines. Combining in vivo EP with plasmid chemokine adjuvants that similarly recruited APCs to the injection site, however, did not result in synergy.

scholarly journals Resistance to Acute Babesiosis Is Associated with Interleukin-12- and Gamma Interferon-Mediated Responses and Requires Macrophages and Natural Killer Cells

2003 ◽  
Vol 71 (4) ◽  
pp. 2002-2008 ◽  
Author(s):  
Irma Aguilar-Delfin ◽  
Peter J. Wettstein ◽  
David H. Persing
Keyword(s):  
Nk Cells ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
No Production ◽  
Cytokine Responses ◽  
Early Production ◽  
Ifn Γ ◽  
Crucial Part

ABSTRACT We examined the role of the cytokines gamma interferon (IFN-γ) and interleukin-12 (IL-12) in the model of acute babesiosis with the WA1 Babesia. Mice genetically deficient in IFN-γ-mediated responses (IFNGR2KO mice) and IL-12-mediated responses (Stat4KO mice) were infected with the WA1 Babesia, and observations were made on the course of infection and cytokine responses. Levels of IFN-γ and IL-12 in serum increased 24 h after parasite inoculation. The augmented susceptibility observed in IFNGR2KO and Stat-4KO mice suggests that the early IL-12- and IFN-γ-mediated responses are involved in protection against acute babesiosis. Resistance appears to correlate with an increase in nitric oxide (NO) production. In order to assess the contribution of different cell subsets to resistance against the parasite, we also studied mice lacking B cells, CD4+ T cells, NK cells, and macrophages. Mice genetically deficient in B lymphocytes or CD4+ T lymphocytes were able to mount protective responses comparable to those of immunosufficient mice. In contrast, in vivo depletion of macrophages or NK cells resulted in elevated susceptibility to the infection. Our observations suggest that a crucial part of the response that protects from the pathogenic Babesia WA1 is mediated by macrophages and NK cells, probably through early production of IL-12 and IFN-γ, and induction of macrophage-derived effector molecules like NO.

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