Nobuyoshi Kitaichi, MD, PhD Schepens Eye Research Institute 20 Staniford Street Boston, MA 02114 Tel.: (617) 912-7453 Fax.: (617) 912-0113 E-Mail: nobukita@vision.eri.harvard.edu Sponsor Andrew W. Taylor, PhD awtaylor@vision.eri.harvard.edu

"I am honored to have been selected for this program, and it has been a wonderful experience. Let me take this opportunity of thanking my mentor and all the fellows, and associates I have had the pleasure to work with."

Studies into the natural induction of Treg cells

Aqueous humor, through alpha-melanocyte stimulating hormone (alpha-MSH), induces the activation of regulatory T (Treg) cells. We examined the possibility that the limited and non-relapsing nature of autoimmune disease in mouse eyes involved the ocular mechanisms of immunosuppression. We found CD4⁺ Treg cells in the spleens of mice recovering from experimental autoimmune uveoretinitis (EAU) in both B10.RIII and C57BL/6 mouse models of EAU. These Treg cells are ocular autoantigen specific and when adoptively transferred into other EAU-susceptible mice suppress the incidence and severity of uveoretinitis. The presence of these Treg cells was dependent on an intact eye and the expression of an alpha-MSH receptor, MC5r. All mice recovered from EAU despite whether they could induce these Treg cells or not (MC5r knockout mice).

These results indicate that ocular tissues re-impose immunosuppression to mediate recovery from autoimmune uveitis. This is not dependent on the induction of Treg cells. Since the byproduct of the ocular microenvironment re-imposing immunosuppression is dependent on the activity of the aqueous humor factor alpha-MSH, it suggests that the mechanism of recovery is through the expression of immunosuppressive factors we normally find in aqueous humor.

Publications

Kitaichi N, Kotake S, Morohashi T, Onoe K, Ohno S, Taylor AW
Diminuition of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells.
J Leukoc Bio. 2002 Dec;72(6):1117-1121.

Namba K, Kitaichi N, Nishida T, Taylor AW
Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte-stimulating hormone and transforming growth factor-beta2
J Leukoc Bio. 2002 Nov;72(5):946-52.

Kitaichi N , Kotake S, Sasamoto Y, Namba K, Matsuda A, Ogasawara K, Onoe K, Matsuda H, Nishihira J. Prominent increase of macrophage migration inhibitory factor in the sera of patients with uveitis. Invest Ophthalmol Vis Sci. 1999; 40: 247.

Kitaichi N , Kotake S, Mizue Y, Matsuda H, Onoe K, Nishihira J. Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis. Brit J Ophthalmol. 2000; 84: 1423.

Kitaichi N , Matsuda A, Kotake S, Namba K, Tagawa Y, Sasamoto Y, Ogasawara K, Iwabuchi K, Onoe K, Matsuda H, Nishihira J. Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies. Curr Eye Res. 2000; 20: 109.

Kitaichi N , Ogasawara K, Iwabuchi K, Nishihira J, Namba K, Onoe K, Konishi J, Kotake S, Matsuda H, Onoe K. Different influence of macrophage migration inhibitory factor (MIF) in signal transduction pathway of various T cell subsets. Immunobiology. 2000; 201: 356.

Kitaichi N , Kotake S, Mizue Y, Sasamoto Y, Goda C, Iwabuchi K, Onoe K, Matsuda H, Nishihira J. High-dose corticosteroid administration induces increase of serum macrophage migration inhibitory factor in patients with Vogt-Koyanagi-Harada´s disease. Microbiol Immunol. 2000; 44: 1075.

Namba K, Ogasawara K, Kitaichi N Matsuki N, Takahashi A, Sasamoto Y, Kotake S, Matsuda H, Iwabuchi K, Ohno S, Onoe K. Identification of a peptide inducing experimental autoimmune uveoretinitis (EAU) in H-2A^k-carrying mice. Clin Exp Immunol. 1998; 111: 442.

Namba K, Ogasawara K, Kitaichi N , Morohashi T, Sasamoto Y, Kotake S, Matsuda H, Iwabuchi K, Ohno S, Onoe K. Amelioration of experimental autoimmune uveoretinitis (EAU) by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand mAb. J Immunol. 2000; 165: 2962.

Morohashi T, Ogasawara K, Kitaichi N , Iwabuchi K, Onoe K. Abrogation of negative selection by GVHR induced by minor histocompatibility antigens or H-2D antigen alone. Immunobiology. 2000; 202: 268.

Morohashi T, Ogasawara K, Kitaichi N , Iwabuchi K, Onoe K. Significant MLR but not CTL responses against recipient antigens generated in T cells from bone marrow chimeras recovered from GVHD. Bone Marrow Transpl. 2000; 26: 1069.

Ito D, Ogasawara K, Matsushita K, Morohashi T, Namba K, Matsuki N, Kitaichi N , Inuyama Y, Hosokawa M, Nakayama E, Iwabuchi K, Onoe K. Effective priming of cytotoxic T lymphocyte precursors by subcutaneous administration of peptide antigens in liposomes accompanied by anti-CD40 and anti-CTLA-4 antibodies. Immunobiology. 2000; 201: 527.

Namba K, Kitaichi N , Nishida T, Taylor AW. Induction of regulatory T cells by the immunomodulating cytokines alpha-melanocyte stimulating hormone and transforming growth factor-beta2. J Leukoc Biol. 2002; in press.

Kitaichi N , Kotake S, Morohashi T, Onoe K, Ohno S, Taylor AW. Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells. Submitted

Namba K, Kotake S, Sasamoto Y, Kitaichi N , Matsuda H, Ogasawara K, Onoe K. Identification of an uveitogenic epitope of Interphotoreceptor Retinoid-Binding protein (IRBP) in mice. Uveitis Today. 1998; 35.

Kotake S, Kitaichi N , Ohno S. Macrophage migration inhibitory factor in uveitis. Int Ophthalmol Clin. 2002; 42: 99.

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Last updated: January 21, 2003