| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Graduate Program in Immunology and
Department of Ophthalmology, University of Texas Southwesterm Medical Center, Dallas, TX 75235
Immune privilege within the eye is due in large part to Ag-specific, systemic down-regulation of Th1 immune responses, a phenomenon termed anterior chamber-associated immune deviation (ACAID). Since the cytokine milieu influences Th cell differentiation, we hypothesized that TGF-ß, an immunosuppressive cytokine secreted by ocular cells, determines the nature of the immune response to Ags introduced into the anterior chamber. Accordingly, an in vitro model of the eye was used to determine the cytokine profile of ocular APC. TGF-ß preferentially induced APC to secrete a Th2-type cytokine, IL-10, and concomitantly suppressed the production of the Th1-inducing cytokine, IL-12. APC incubated with TGF-ß and anti-IL-10 Ab lost their ability to induce ACAID. In the absence of TGF-ß, Ag-pulsed APC preferentially secreted IL-12 and elicited Ag-specific Th1 responses (i.e., delayed-type hypersensitivity (DTH)). However, APC pulsed with Ag and exogenous IL-10 behaved in a manner similar to ocular APC and induced Ag-specific suppression of DTH. The role of IL-10 in ACAID was confirmed in IL-10 knockout mice. Anterior chamber injection of OVA into IL-10 knockout mice elicited normal DTH responses rather than ACAID. Moreover, Ag-pulsed APC from IL-10 knockout mice were unable to induce ACAID following in vitro treatment with TGF-ß. Thus, TGF-ß predisposes ocular APC to secrete IL-10 during Ag processing. This, in turn, directs the immune response away from a Th1 pathway and toward a Th2-like response in which DTH is suppressed.
This article has been cited by other articles:
|
|
 |
|
  H. Qiao, K. Lucas, and J. Stein-Streilein Retinal Laser Burn Disrupts Immune Privilege in the Eye Am. J. Pathol., February 1, 2009; 174(2): 414 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Watte, T. Nakamura, C. H. Lau, J. R. Ortaldo, and J. Stein-Streilein Ly49 C/I-dependent NKT cell-derived IL-10 is required for corneal graft survival and peripheral tolerance J. Leukoc. Biol., April 1, 2008; 83(4): 928 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Langmann Microglia activation in retinal degeneration J. Leukoc. Biol., June 1, 2007; 81(6): 1345 - 1351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Ashour and J. Y. Niederkorn {gamma}{delta} T Cells Promote Anterior Chamber-Associated Immune Deviation and Immune Privilege through Their Production of IL-10 J. Immunol., December 15, 2006; 177(12): 8331 - 8337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Meng, P. Yang, B. Li, H. Zhou, X. Huang, L. Zhu, Y. Ren, and A. Kijlstra CD4+PD-1+ T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Deviation. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4444 - 4452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Ashour and J. Y. Niederkorn Peripheral Tolerance Via the Anterior Chamber of the Eye: Role of B Cells in MHC Class I and II Antigen Presentation J. Immunol., May 15, 2006; 176(10): 5950 - 5957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Toscano, A. G. Commodaro, J. M. Ilarregui, G. A. Bianco, A. Liberman, H. M. Serra, J. Hirabayashi, L. V. Rizzo, and G. A. Rabinovich Galectin-1 Suppresses Autoimmune Retinal Disease by Promoting Concomitant Th2- and T Regulatory-Mediated Anti-Inflammatory Responses J. Immunol., May 15, 2006; 176(10): 6323 - 6332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-L. Cheng, H.-W. Chen, J.-P. Tsai, Y.-P. Lee, Y.-C. Shih, C.-M. Chang, and C.-C. Ting Clonal restriction of the expansion of antigen-specific CD8+ memory T cells by transforming growth factor-{beta} J. Leukoc. Biol., May 1, 2006; 79(5): 1033 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Masli, B. Turpie, and J W. Streilein Thrombospondin orchestrates the tolerance-promoting properties of TGF{beta}-treated antigen-presenting cells Int. Immunol., May 1, 2006; 18(5): 689 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Keino, S. Masli, S. Sasaki, J. W. Streilein, and J. Stein-Streilein CD8+ T Regulatory Cells Use a Novel Genetic Program that Includes CD103 to Suppress Th1 Immunity in Eye-Derived Tolerance. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1533 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jiang and L. Chess Regulation of immune responses by T cells. N. Engl. J. Med., March 16, 2006; 354(11): 1166 - 1176. [Full Text] [PDF]
|
|
|
|
 |
|
 D.-B. Borza, O. Bondar, S. Colon, P. Todd, Y. Sado, E. G. Neilson, and B. G. Hudson Goodpasture Autoantibodies Unmask Cryptic Epitopes by Selectively Dissociating Autoantigen Complexes Lacking Structural Reinforcement: NOVEL MECHANISMS FOR IMMUNE PRIVILEGE AND AUTOIMMUNE PATHOGENESIS J. Biol. Chem., July 22, 2005; 280(29): 27147 - 27154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Beauregard, C. Stevens, E. Mayhew, and J. Y. Niederkorn Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection J. Immunol., June 1, 2005; 174(11): 6577 - 6581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kitaichi, K. Namba, and A. W. Taylor Inducible immune regulation following autoimmune disease in the immune-privileged eye J. Leukoc. Biol., April 1, 2005; 77(4): 496 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Graner, A. Likhacheva, J. Davis, A. Raymond, J. Brandenberger, A. Romanoski, S. Thompson, E. Akporiaye, and E. Katsanis Cargo from Tumor-Expressed Albumin Inhibits T-Cell Activation and Responses Cancer Res., November 1, 2004; 64(21): 8085 - 8092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Y. Niederkorn, E. Mayhew, J. Mellon, and S. Hegde Role of Tumor Necrosis Factor Receptor Expression in Anterior Chamber-Associated Immune Deviation (ACAID) and Corneal Allograft Survival Invest. Ophthalmol. Vis. Sci., August 1, 2004; 45(8): 2674 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Loskog, H. Dzojic, S. Vikman, C. Ninalga, M. Essand, O. Korsgren, and T. H. Totterman Adenovirus CD40 Ligand Gene Therapy Counteracts Immune Escape Mechanisms in the Tumor Microenvironment J. Immunol., June 1, 2004; 172(11): 7200 - 7205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Bonecini-Almeida, J. L. Ho, N. Boechat, R. C. Huard, S. Chitale, H. Doo, J. Geng, L. Rego, L. C. O. Lazzarini, A. L. Kritski, et al. Down-Modulation of Lung Immune Responses by Interleukin-10 and Transforming Growth Factor {beta} (TGF-{beta}) and Analysis of TGF-{beta} Receptors I and II in Active Tuberculosis Infect. Immun., May 1, 2004; 72(5): 2628 - 2634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kosiewicz, P. Alard, S. Liang, and S. L Clark Mechanisms of tolerance induced by transforming growth factor-{beta}-treated antigen-presenting cells: CD8 regulatory T cells inhibit the effector phase of the immune response in primed mice through a mechanism involving Fas ligand Int. Immunol., May 1, 2004; 16(5): 697 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. F. H. M. Boonman, G. J. D. van Mierlo, M. F. Fransen, K. L. M. C. Franken, R. Offringa, C. J. M. Melief, M. J. Jager, and R. E. M. Toes Intraocular Tumor Antigen Drains Specifically to Submandibular Lymph Nodes, Resulting in an Abortive Cytotoxic T Cell Reaction J. Immunol., February 1, 2004; 172(3): 1567 - 1574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Skelsey, E. Mayhew, and J. Y. Niederkorn Splenic B Cells Act as Antigen Presenting Cells for the Induction of Anterior Chamber-Associated Immune Deviation Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5242 - 5251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Lund, S. J. Ono, D. J. Keegan, and J. M. Lawrence Retinal transplantation: progress and problems in clinical application J. Leukoc. Biol., August 1, 2003; 74(2): 151 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Dick, D. Carter, M. Robertson, C. Broderick, E. Hughes, J. V. Forrester, and J. Liversidge Control of myeloid activity during retinal inflammation J. Leukoc. Biol., August 1, 2003; 74(2): 161 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Streilein Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation J. Leukoc. Biol., August 1, 2003; 74(2): 179 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Rezai, L. Farrokh-Siar, E. M. Gasyna, J. T. Ernest, and G. A. van Seventer The Effect of Type I and II Interferons on Human Fetal Retinal Pigment Epithelium-Induced Apoptosis in Jurkat T Cells Invest. Ophthalmol. Vis. Sci., July 1, 2003; 44(7): 3130 - 3134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D A Carter and A D Dick Lipopolysaccharide/interferon-{gamma} and not transforming growth factor {beta} inhibits retinal microglial migration from retinal explant Br J Ophthalmol, April 1, 2003; 87(4): 481 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Okura, Y. Jee, and Y. Matsumoto Acquired thymic tolerance to autoimmune encephalomyelitis is associated with activation of peripheral IL-10-producing macrophages/dendritic cells Int. Immunol., March 1, 2003; 15(3): 437 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. L. Woodward, S. R. Elshaw, A. K. Murray, C. E. Nichols, N. Cross, D. Laws, I. G. Rennie, and K. Sisley Stimulation and Inhibition of Uveal Melanoma Invasion by HGF, GRO, IL-1{alpha} and TGF-{beta} Invest. Ophthalmol. Vis. Sci., October 1, 2002; 43(10): 3144 - 3152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rutella, L. Pierelli, G. Bonanno, S. Sica, F. Ameglio, E. Capoluongo, A. Mariotti, G. Scambia, G. d'Onofrio, and G. Leone Role for granulocyte colony-stimulating factor in the generation of human T regulatory type 1 cells Blood, September 18, 2002; 100(7): 2562 - 2571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Gregerson and C. Dou Spontaneous Induction of Immunoregulation by an Endogenous Retinal Antigen Invest. Ophthalmol. Vis. Sci., September 1, 2002; 43(9): 2984 - 2991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Brissette-Storkus, S. M. Reynolds, A. J. Lepisto, and R. L. Hendricks Identification of a Novel Macrophage Population in the Normal Mouse Corneal Stroma Invest. Ophthalmol. Vis. Sci., July 1, 2002; 43(7): 2264 - 2271. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Katagiri, J. Zhang-Hoover, J. S. Mo, J. Stein-Streilein, and J. W. Streilein Using Tolerance Induced Via the Anterior Chamber of the Eye to Inhibit Th2-Dependent Pulmonary Pathology J. Immunol., July 1, 2002; 169(1): 84 - 89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sanchez-Torres, G. S. Garcia-Romo, M. A. Cornejo-Cortes, A. Rivas-Carvalho, and G. Sanchez-Schmitz CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells Int. Immunol., December 1, 2001; 13(12): 1571 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Bunn, P. J. Parsons, E. Kao, and R. R. Dietert Exposure to Lead during Critical Windows of Embryonic Development: Differential Immunotoxic Outcome Based on Stage of Exposure and Gender Toxicol. Sci., November 1, 2001; 64(1): 57 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Terui, K. Sano, H. Shirota, N. Kunikata, M. Ozawa, M. Okada, M. Honda, G. Tamura, and H. Tagami TGF-{beta}-Producing CD4+ Mediastinal Lymph Node Cells Obtained from Mice Tracheally Tolerized to Ovalbumin (OVA) Suppress Both Th1- and Th2-Induced Cutaneous Inflammatory Responses to OVA by Different Mechanisms J. Immunol., October 1, 2001; 167(7): 3661 - 3667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-C. Sheu, R.-H. Lin, H.-C. Lien, H.-N. Ho, S.-M. Hsu, and S.-C. Huang Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer J. Immunol., September 1, 2001; 167(5): 2972 - 2978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, I. Goldschneider, J. O’Rourke, and R. E. Cone Blood mononuclear cells induce regulatory NK T thymocytes in anterior chamber-associated immune deviation J. Leukoc. Biol., May 1, 2001; 69(5): 741 - 746. [Abstract] [Full Text]
|
|
|
|
|
|
M. E. Skelsey, J. Mellon, and J. Y. Niederkorn {{gamma}}{{delta}}T Cells Are Needed for Ocular Immune Privilege and Corneal Graft Survival J. Immunol., April 1, 2001; 166(7): 4327 - 4333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-T. Yan, M. Zhuang, J. E. Oakes, and R. N. Lausch Autocrine action of IL-10 suppresses proinflammatory mediators and inflammation in the HSV-1-infected cornea J. Leukoc. Biol., January 1, 2001; 69(1): 149 - 157. [Abstract] [Full Text]
|
|
|
|
|
|
K.-H. Sonoda, D. E. Faunce, M. Taniguchi, M. Exley, S. Balk, and J. Stein-Streilein NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance J. Immunol., January 1, 2001; 166(1): 42 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. da Costa, C. L. Yasuda, S. M Scagliusi, B. M. Diaz-Bardales, E. Maciel, B. P Damasceno, M H. S. Blotta, C. P Tilbery, and L. M. Santos pattern of cytokine secretion by peripheral blood cells of patients with multiple sclerosis in Brazil Multiple Sclerosis, October 1, 2000; 6(5): 293 - 299. [Abstract] [PDF]
|
|
|
|
|
|
S. Hegde and J. Y. Niederkorn The Role of Cytotoxic T Lymphocytes in Corneal Allograft Rejection Invest. Ophthalmol. Vis. Sci., October 1, 2000; 41(11): 3341 - 3347. [Abstract] [Full Text]
|
|
|
|
|
|
C. Broderick, L. Duncan, N. Taylor, and A. D. Dick IFN-{gamma} and LPS-Mediated IL-10-Dependent Suppression of Retinal Microglial Activation Invest. Ophthalmol. Vis. Sci., August 1, 2000; 41(9): 2613 - 2622. [Abstract] [Full Text]
|
|
|
|
|
|
C. H. Little, G. M. Georgiou, A. Marceglia, H. Ogedgebe, R. E. Cone, and D. Mazza Measurement of T-Cell-Derived Antigen Binding Molecules and Immunoglobulin G Specific to Candida albicans Mannan in Sera of Patients with Recurrent Vulvovaginal Candidiasis Infect. Immun., July 1, 2000; 68(7): 3840 - 3847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. X. Zhu, S. Sharma, M. Stolina, B. Gardner, M. D. Roth, D. P. Tashkin, and S. M. Dubinett {Delta}-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway J. Immunol., July 1, 2000; 165(1): 373 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kezuka and J. W. Streilein In Vitro Generation of Regulatory CD8+ T Cells Similar to those Found in Mice with Anterior Chamber-Associated Immune Deviation Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1803 - 1811. [Abstract] [Full Text]
|
|
|
|
|
|
A. A. Bickerstaff, D. Xia, R. P. Pelletier, and C. G. Orosz Mechanisms of Graft Acceptance: Evidence That Plasminogen Activator Controls Donor-Reactive Delayed-Type Hypersensitivity Responses in Cardiac Allograft Acceptor Mice J. Immunol., May 15, 2000; 164(10): 5132 - 5139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. de Vos, A. Fukushima, M. C. Lobanoff, B. P. Vistica, J. C. Lai, J.-C. Grivel, E. F. Wawrousek, S. M. Whitcup, and I. Gery Breakdown of Tolerance to a Neo-Self Antigen in Double Transgenic Mice in Which B Cells Present the Antigen J. Immunol., May 1, 2000; 164(9): 4594 - 4600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sato, H. Kawasaki, H. Nagayama, M. Enomoto, C. Morimoto, K. Tadokoro, T. Juji, and T. A. Takahashi TGF-{beta}1 Reciprocally Controls Chemotaxis of Human Peripheral Blood Monocyte-Derived Dendritic Cells Via Chemokine Receptors J. Immunol., March 1, 2000; 164(5): 2285 - 2295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Wendling, L. Paul, R. van der Zee, B. Prakken, M. Singh, and W. van Eden A Conserved Mycobacterial Heat Shock Protein (hsp) 70 Sequence Prevents Adjuvant Arthritis upon Nasal Administration and Induces IL-10-Producing T Cells That Cross-React with the Mammalian Self-hsp70 Homologue J. Immunol., March 1, 2000; 164(5): 2711 - 2717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-H. Sonoda, M. Exley, S. Snapper, S. P. Balk, and J. Stein-Streilein Cd1-Reactive Natural Killer T Cells Are Required for Development of Systemic Tolerance through an Immune-Privileged Site J. Exp. Med., November 1, 1999; 190(9): 1215 - 1226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Dick, K. Siepmann, C. Dees, L. Duncan, C. Broderick, J. Liversidge, and J. V. Forrester Fas-Fas Ligand-Mediated Apoptosis within Aqueous during Idiopathic Acute Anterior Uveitis Invest. Ophthalmol. Vis. Sci., September 1, 1999; 40(10): 2258 - 2267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishida and A. W. Taylor Specific Aqueous Humor Factors Induce Activation of Regulatory T Cells Invest. Ophthalmol. Vis. Sci., September 1, 1999; 40(10): 2268 - 2274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Laliotou and A. D Dick Modulating phenotype and cytokine production of leucocytic retinal infiltrate in experimental autoimmune uveoretinitis following intranasal tolerance induction with retinal antigens Br J Ophthalmol, April 1, 1999; 83(4): 478 - 485. [Abstract] [Full Text]
|
|
|
|
|
|
J. F. Rowell and D. E. Griffin The Inflammatory Response to Nonfatal Sindbis Virus Infection of the Nervous System Is More Severe in SJL Than in BALB/c Mice and Is Associated with Low Levels of IL-4 mRNA and High Levels of IL-10-Producing CD4+ T Cells J. Immunol., February 1, 1999; 162(3): 1624 - 1632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kosiewicz, P. Alard, and J. W. Streilein Alterations in Cytokine Production Following Intraocular Injection of Soluble Protein Antigen: Impairment in IFN-{gamma} and Induction of TGF-{beta} and IL-4 Production J. Immunol., November 15, 1998; 161(10): 5382 - 5390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Piccirillo, Y. Chang, and G. J. Prud'homme TGF-{beta}1 Somatic Gene Therapy Prevents Autoimmune Disease in Nonobese Diabetic Mice J. Immunol., October 15, 1998; 161(8): 3950 - 3956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Hellstrom, J. A. Ledbetter, N. Scholler, Y. Yang, Z. Ye, G. Goodman, J. Pullman, M. Hayden-Ledbetter, and K. E. Hellstrom CD3-mediated activation of tumor-reactive lymphocytes from patients with advanced cancer PNAS, June 5, 2001; 98(12): 6783 - 6788. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
