| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Laboratory of Immunology and the 2 Laboratory of Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
METHODS. H-2b (C57BL/6, 129/J) and H-2r (B10.RIII) mice were immunized with peptide 1-20 or with whole (bovine) IRBP. EAU (histopathology) and immunologic responses (delayed-type hypersensitivity [DTH], lymphocyte proliferation, and cytokine production) were assessed after 21 days.
RESULTS. C57BL/6 mice, 129/J and (129/JxC57BL/6)F1 mice, immunized with 200 to
300 µg of peptide, developed DTH and EAU with scores comparable to
those induced by 100 µg IRBP. Their lymphocytes proliferated to the
peptide and produced interferon-
(but not interleukin-4) and
transferred EAU to syngeneic recipients. Lymphocytes of IRBP-immunized
mice also responded to the peptide. Peptide 1-20–immunized B10.RIII
mice failed to develop either disease or immunologic responses.
CONCLUSIONS. Human IRBP peptide 1-20 contains a major epitope for the H-2b haplotype, which is apparently not presented by the H-2r haplotype.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
EAU is induced in animals by immunization with retinal antigens or by the adoptive transfer of retinal antigen-specific T lymphocytes.2 3 Among the ocular antigens known to induce EAU in rodent models are the retinal interphotoreceptor retinoid–binding protein (IRBP) and the soluble retinal antigen (S–antigen) also referred to as arrestin.1 Although both S–antigen and IRBP have been identified as major autoantigens of the retina, the latter proved to be a superior uveitopathogen in the mouse model.
IRBP is a 140-kDa glycolipoprotein residing in the interphotoreceptor matrix between the neural retina and the retinal pigment epithelium.4 5 It consists of a fourfold repeat structure with 30% to 40% amino acid sequence homology shared among the repeats and is evolutionarily conserved among species, with approximately 80% sequence homology at the amino acid level between the bovine and the human.4 5
As in some human uveitic diseases that have strong HLA associations, susceptibility to EAU in the murine models is also in part controlled by the major histocompatibility complex (MHC).6 Provided that a "permissive" (e.g., B10) genetic background is present, mice of the haplotypes H-2r, H-2k, and H-2b develop EAU after immunization with IRBP, whereas many other haplotypes are resistant.6 The MHC control of EAU was tentatively mapped to the I-A subregion (homologous to human HLA-DQ), implicating epitope recognition. Epitopes that induce EAU in the H-2r and H-2k haplotypes have been described previously.7 8 In the present study, we show that peptide 1-20 of human IRBP is immunogenic and pathogenic in H-2b-mice (C57BL/6, 129/J). This finding enhances the usefulness of the EAU model by facilitating utilization of the numerous gene-manipulated (transgenic and knockout) strains available on the C57BL/6 and 129 backgrounds.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Reagents
Human IRBP peptide 1-20 (GPTHLFQPSLVLDMAKVLLD) and its truncated
peptide 6-20 derivative were synthesized on an Applied Biosystems 432A
Peptide Synthesizer using Fmoc Chemistry. Purified Bordetella
pertussis toxin (PTX) was from Sigma Chemical (St. Louis, MO), and
complete Freund’s adjuvant (CFA) was from Difco (Detroit, MI). IRBP
was isolated from bovine retinas, as described previously, using Con
A–Sepharose affinity chromatography and fast performance liquid
chromatography.5
IRBP preparations were aliquoted and
stored at -70°C.
Induction and Scoring of EAU
Mice were immunized subcutaneously in both thighs and base of tail
with the peptide, in 0.2 ml emulsion in CFA (1:1, vol/vol) that had
been supplemented with Mycobacterium tuberculosis strain
H37RA to 2.5 mg/ml, and were given 1.5 µg of PTX intraperitoneally as
additional adjuvant. Tissues (eyes and lymphoid organs) were collected
on day 21 after immunization.
For induction of EAU by adoptive transfer of primed cells, donor C57BL/6 mice were immunized with the peptide (150 µg/mouse) as above. Lymph node and spleen cells collected on day 14 after immunization were pooled, and the cell suspension was adjusted to 107 cells/ml in culture medium. The cell cultures were stimulated with the peptide (5 µM) and were incubated for 72 hours in 75-cm3 flasks. To remove excess adherent cells (macrophages), the cultures were transferred into new flasks after 24 hours and again after 48 hours. At the end of the incubation period, the cells were harvested, washed, and injected intraperitoneally (40–50 x 106 cells/mouse) into naive C57BL/6 mice. EAU was assessed by histopathology 14 days after the adoptive transfer.
Freshly enucleated eyes were prefixed for 1 hour in phosphate-buffered glutaraldehyde (4%), postfixed in phosphate-buffered formaldehyde (10%) at least overnight, and embedded in glycol methacrylate. Sections (3–6 µm) were stained with hematoxylin–eosin. Incidence and severity of the disease were examined for each eye, in a masked fashion by one of us (C-CC) and scored on a scale of 0 to 4 in half-point increments, according to a semiquantitative system described previously.9
DTH Assay
On day 19 after immunization, mice were injected intradermally
with 10 µg of the peptide suspended in phosphate buffered
saline (PBS), into the pinna of one ear. The other ear was injected
with PBS. Ear swelling was measured after 48 hours with a spring-loaded
micrometer. Antigen-specific DTH was measured as the difference in ear
thickness before and after challenge.
Lymphocyte Proliferation
Primed lymphocytes obtained from draining lymph nodes (inguinals
and iliacs) and spleens were suspended at 5 x
105 cells per 0.2 ml of RPMI 1640 medium
supplemented with 2 mM L-glutamine, 5 x
10-5 M 2-mercaptoethanol, 0.1 mM nonessential
amino acids, 1 mM sodium pyruvate, and 1% normal mouse serum.
Triplicate 0.2-ml cultures in 96-well round-bottomed plates (Nunc) were
stimulated with the specified peptide at the indicated concentration.
The cultures were incubated for 72 hours at 37°C in 5%
CO2 in air, pulsed with 1 µCi
[3H]-thymidine (New England Nuclear, Boston,
MA) per well during the last 18 hours of incubation, and then were
harvested using a PHD cell harvester (Cambridge Technology,
Watertown, MA). [3H]-thymidine uptake was determined by
standard liquid scintillation.
Cytokine Assays
Lymph node and spleen cells were cultured in 96-well flat-bottomed
plates (1 x 106 cells/0.2 ml culture
medium/well) either alone or with the peptide (3 µM) as above.
Supernatants were collected after 24 hours for detection of interleukin
(IL)-2 and after 48 hours for detection of other cytokines, and were
kept frozen in small aliquots at -20°C. Cytokine production was
measured by the enzyme-linked immunosorbent assay (ELISA) antibody
pairs from Pharmingen (La Jolla, CA) for IL-2, IL-4, and IL-6, and from
Endogen (Boston, MA) for interferon (IFN)- and IL-5, as previously
described.10
Tumor necrosis factor (TNF)-
was
determined by the murine cytokine ELISA detection kit (R&D,
Minneapolis, MN), whereas IL-10 and IL-12p40 were determined by the
kits from Genzyme (Cambridge, MA).
Statistical Analyses and Reproducibility
Experiments were repeated at least two and usually three times.
Response patterns were highly reproducible. Statistical analyses for
parametric data (DTH, proliferation, and cytokine production) were
performed by independent t-test. For nonparametric data (EAU
scores) analysis was by the Snedecor and Cochran’s11
test
for linear trends in proportions.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
|
Figure 2A illustrates the ocular histopathology of C57BL/6 mice immunized with peptide 1-20 (300 µg/mouse). Inflammatory cell infiltrates were present in the vitreous, the retina, and the choroid. Damage to the photoreceptor layer, retinal folding, and retinal vasculitis were also observed. No ocular abnormalities were seen in B10.RIII mice immunized with the peptide (up to 300 µg/mouse; Fig. 2B ).
|
|
To determine whether peptide 1-20 is recognized in the context of the
whole IRBP molecule, C57BL/6 mice were immunized either with whole
bovine IRBP or with the peptide. The ability of primed T cells to mount
a recall response in vitro to the immunizing and the nonimmunizing
antigen was determined. Lymphocytes from IRBP-immunized mice did
proliferate to peptide 1-20; however, lymphocytes of mice immunized
with the peptide proliferated only against the peptide but not against
whole IRBP (data not shown). Nevertheless, as stated above, weak
cross-reactivity peptide 
IRBP was detectable at the level of DTH.
Higher sensitivity of DTH in comparison to proliferation for detecting
borderline responses has been noted by us previously.7
Lymph node and spleen cells obtained from C57BL/6 mice immunized with
150 µg of the peptide and cultured with the peptide secreted
significant amounts of IFN- (42,110 and 49,770 pg/ml, respectively).
The pattern of cytokine production differed only slightly between the
two organs, with splenocytes producing more IL-2 (7.09 U/ml compared
with 1.68 U/ml in the lymph nodes) but less TNF- (99 and 147 pg/ml,
respectively). There was no detectable production of IL-4, IL-5, IL-6,
or IL-10 by lymph node cells and minimal production of IL-4 (336
pg/ml), IL-5 (190 pg/ml), and IL-6 (361 pg/ml) by spleen cells.
Interestingly, a spontaneous release of IL-12p40 by unstimulated cells
was noted (approximately 348 pg/ml in the lymph nodes and 588 pg/ml in
the spleen), which was suppressed in the presence of the peptide
(P < 0.0025). This phenomenon was reproducible in
three separate experiments and was consistent under various
concentrations of the peptide. These data taken together indicate that
the cytokine production associated with peptide 1-20 is consistent with
a Th-1 dominant profile.
Adoptive Transfer of EAU by Primed Lymphocytes Stimulated with
Peptide 1-20
Lymph nodes and splenocytes from C57BL/6 donors primed with
peptide 1-20 were cultured with the peptide for 72 hours, and 40 to
50 x 106 cells were adoptively transferred
into naive syngeneic mice. The peptide-stimulated cells were able to
induce EAU in 50% to 60% of naive recipients, with disease scores of
0.5 to 1.0, which is within the same range as actively immunized
animals (Fig. 1B)
. Ocular histopathology of the adoptively transferred
animals (Fig. 2C)
showed typical inflammatory cell infiltration in the
subretinal space and the retina, some retinal folds, and numerous foci
of photoreceptor damage. Vitritis and choroiditis were also observed.
Role of the Propeptide in Epitope Recognition
Native murine IRBP has not hitherto been N-terminal sequenced;
therefore, it is not certain whether its mature form contains the
propeptide sequence (residues 1–5) as tentatively shown in Figure 1A .
We, therefore, immunized C57BL/6 mice with a truncated version of the
peptide, lacking the first 5 residues. The truncated version was poorly
immunogenic as judged by lymphocyte proliferation and was unable to
induce EAU at doses up to 300 µg in C57BL/6 mice, whereas positive
controls immunized with peptide 1-20 mounted proliferative responses
and developed EAU with the expected scores and incidence (Fig. 4)
. This strongly suggests that the propeptide sequence is required for
immunogenicity and for recognition of the autologous mouse IRBP.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Peptide 1-20 is both immunogenic and pathogenic in C57BL/6 and 129/J mice and their F1 hybrids (all of which share the H-2b haplotype). In contrast, B10.RIII (H-2r) mice largely failed to respond to the peptide, as evidenced by the virtual lack of a DTH response and cellular proliferation. Judging by its lack of immunogenicity, the reason underlying the resistance of B10.RIII mice to EAU induction by peptide 1-20 could be either poor binding to MHC or could reflect a "hole" in the T-cell repertoire (TCR; i.e., lack of peripheral T cells bearing TCRs capable of recognizing the peptide). This contrasts with the situation described for the response of non–H-2r strains to the H-2r–specific peptide 161-180, which, although resistant to disease, do develop immunologic responses to the peptide.7
Unlike the human and bovine proteins,12 13 the N-terminal sequence of mouse IRBP has not been elucidated at the protein level. Thus, it was not clear whether mature mouse IRBP retains the propeptide sequence, similarly to humans, or not, as in cattle. Our finding that the truncated peptide, lacking residues 1 to 5, is nonpathogenic and is poorly immunogenic in C57BL/6 mice, indicates that these residues are required for immunologic recognition of the autologous target sequence, and as a corollary, that at least a proportion of the mature murine IRBP molecules must contain the propeptide. This finding provides an interesting example of how immunologic methods might be used to draw structural conclusions about a protein that is difficult to obtain in sufficient amounts and purity for N-terminal sequencing. In experiments not reported here, using the alanine substitution method we found that residues 6 to 13 (FQPSLVLD) are important for the recognition of peptide 1-20 by primed H-2b lymphocytes and are likely to contain MHC and TCR contact residues but that alanine substitution of single residues within the propeptide had no effect on lymphocyte recognition of the peptide sequence (Avichezer et al., unpublished observations). We therefore hypothesize that residues 1 to 5 might facilitate MHC/TCR binding by influencing the correct conformation of the peptide, rather than by containing MHC/TCR contact residues.
The major cytokines produced in response to the peptide were IFN-
and IL-2, with little or no detectable production of IL-4 and IL-5.
This profile is consistent with a Th1-dominant response. Although low
amounts of IL-4 were detected in the spleen, they may well represent a
"bystander" effect where non–T cells in the spleen secrete IL-4 in
response to T-cell–produced cytokines (Paul V. Lehmann, Case Western
University, personal communication). Adoptive transfer of cells from
donors primed with peptide 1-20 to naive syngeneic recipients induced
disease. These results are in line with previous studies, which
implicated Th-1–like effector cells in the pathogenesis of EAU and
other tissue-specific autoimmune diseases.14
15
16
In summary, the results of the present study demonstrate that peptide 1-20 of human IRBP is immunogenic and pathogenic in H-2b haplotype mice and that it induces a Th-1–dominant response. The pathology of disease induced by the peptide, or by adoptive transfer of cells specific to the peptide, is similar to that induced by the whole IRBP protein. The peptide is nonpathogenic and nonimmunogenic in B10.RIII mice. The identification of a major uveitogenic epitope for H-2b haplotype mice will facilitate the use of the many gene-manipulated knockout and transgenic mice, which are available on the C57BL/6 and 129 background, for the study of basic mechanisms in immunopathogenesis of uveitic disease.
|
Acknowledgements |
|---|
|
Footnotes |
|---|
Submitted for publication June 3, 1999; revised August 16, 1999; accepted September 3, 1999.
Commercial relationships policy: N.
Corresponding author: Rachel R. Caspi, Laboratory of Immunology, National Eye Institute, NIH, Building 10, Room 10N222, Bethesda, MD 20892-1857. rcaspi{at}helix.nih.gov
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  Y. Cui, H. Shao, C. Lan, H. Nian, R. L. O'Brien, W. K. Born, H. J. Kaplan, and D. Sun Major Role of {gamma}{delta} T Cells in the Generation of IL-17+ Uveitogenic T Cells J. Immunol., July 1, 2009; 183(1): 560 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yoshimura, K.-H. Sonoda, N. Ohguro, Y. Ohsugi, T. Ishibashi, D. J. Cua, T. Kobayashi, H. Yoshida, and A. Yoshimura Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis Rheumatology, April 1, 2009; 48(4): 347 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sugita, S. Horie, O. Nakamura, Y. Futagami, H. Takase, H. Keino, H. Aburatani, N. Katunuma, K. Ishidoh, Y. Yamamoto, et al. Retinal Pigment Epithelium-Derived CTLA-2{alpha} Induces TGF{beta}-Producing T Regulatory Cells J. Immunol., December 1, 2008; 181(11): 7525 - 7536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. E. Raveney, D. A. Copland, L. B. Nicholson, and A. D. Dick Fingolimod (FTY720) as an Acute Rescue Therapy for Intraocular Inflammatory Disease Arch Ophthalmol, October 1, 2008; 126(10): 1390 - 1395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Cortes, M. J. Mattapallil, P. B. Silver, L. A. Donoso, G. I. Liou, W. Zhu, C.-C. Chan, and R. R. Caspi Repertoire Analysis and New Pathogenic Epitopes of IRBP in C57BL/6 (H-2b) and B10.RIII (H-2r) Mice Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1946 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Luger, P. B. Silver, J. Tang, D. Cua, Z. Chen, Y. Iwakura, E. P. Bowman, N. M. Sgambellone, C.-C. Chan, and R. R. Caspi Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category J. Exp. Med., April 14, 2008; 205(4): 799 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Yoshimura, K.-H. Sonoda, Y. Miyazaki, Y. Iwakura, T. Ishibashi, A. Yoshimura, and H. Yoshida Differential roles for IFN-{gamma} and IL-17 in experimental autoimmune uveoretinitis Int. Immunol., February 1, 2008; 20(2): 209 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Peng, G. Han, H. Shao, Y. Wang, H. J. Kaplan, and D. Sun Characterization of IL-17+ Interphotoreceptor Retinoid-Binding Protein-Specific T Cells in Experimental Autoimmune Uveitis Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4153 - 4161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Copland, C. J. Calder, B. J.E. Raveney, L. B. Nicholson, J. Phillips, H. Cherwinski, M. Jenmalm, J. D. Sedgwick, and A. D. Dick Monoclonal Antibody-Mediated CD200 Receptor Signaling Suppresses Macrophage Activation and Tissue Damage in Experimental Autoimmune Uveoretinitis Am. J. Pathol., August 1, 2007; 171(2): 580 - 598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hisatomi, K.-h. Sonoda, F. Ishikawa, H. Qiao, T. Nakazawa, M. Fukata, T. Nakamura, K. Noda, S. Miyahara, M. Harada, et al. Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation Br. J. Ophthalmol., April 1, 2007; 91(4): 520 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-H. Sonoda, T. Yoshimura, A. Takeda, T. Ishibashi, S. Hamano, and H. Yoshida WSX-1 plays a significant role for the initiation of experimental autoimmune uveitis Int. Immunol., January 1, 2007; 19(1): 93 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H Keino, M Takeuchi, Y Usui, T Hattori, N Yamakawa, T Kezuka, J-I Sakai, and M Usui Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis Br. J. Ophthalmol., January 1, 2007; 91(1): 105 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wang, F. Bai, M. Pries, S. Buus, J. U. Prause, and M. H. Nissen Identification of MHC class I h-2 kb/db-restricted immunogenic peptides derived from retinal proteins. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 3939 - 3945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-R. Jiang, L. Hwenda, K. Makinen, C. Oetke, P. R. Crocker, and J. V. Forrester Sialoadhesin Promotes the Inflammatory Response in Experimental Autoimmune Uveoretinitis J. Immunol., August 15, 2006; 177(4): 2258 - 2264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Guyver, D. A. Copland, C. J. Calder, A. Sette, J. Sidney, A. D. Dick, and L. B. Nicholson Mapping Immune Responses to mRBP-3 1-16 Peptide with Altered Peptide Ligands Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 2027 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Calder, L. B. Nicholson, and A. D. Dick A Selective Role for the TNF p55 Receptor in Autocrine Signaling following IFN-{gamma} Stimulation in Experimental Autoimmune Uveoretinitis J. Immunol., November 15, 2005; 175(10): 6286 - 6293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hashida, N. Ohguro, K. Nakai, M. Kobashi-Hashida, S.-i. Hashimoto, K. Matsushima, and Y. Tano Microarray Analysis of Cytokine and Chemokine Gene Expression after Prednisolone Treatment in Murine Experimental Autoimmune Uveoretinitis Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4224 - 4234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shao, Y. Peng, T. Liao, M. Wang, M. Song, H. J. Kaplan, and D. Sun A Shared Epitope of the Interphotoreceptor Retinoid-Binding Protein Recognized by the CD4+ and CD8+ Autoreactive T Cells J. Immunol., August 1, 2005; 175(3): 1851 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Bagenstose, R. K. Agarwal, P. B. Silver, D. M. Harlan, S. C. Hoffmann, R. L. Kampen, C.-C. Chan, and R. R. Caspi Disruption of CD40/CD40-Ligand Interactions in a Retinal Autoimmunity Model Results in Protection without Tolerance J. Immunol., July 1, 2005; 175(1): 124 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Z. Howard, H. F. Dong, S. B. Su, R. R. Caspi, X. Chen, P. Plotz, and J. J. Oppenheim Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate Blood, June 1, 2005; 105(11): 4207 - 4214. [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]
|
|
|
|
|
|
P. Zamiri, S. Masli, N. Kitaichi, A. W. Taylor, and J. W. Streilein Thrombospondin Plays a Vital Role in the Immune Privilege of the Eye Invest. Ophthalmol. Vis. Sci., March 1, 2005; 46(3): 908 - 919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Taylor, K. McConnachie, C. Calder, R. Dawson, A. Dick, J. D. Sedgwick, and J. Liversidge Enhanced Tolerance to Autoimmune Uveitis in CD200-Deficient Mice Correlates with a Pronounced Th2 Switch in Response to Antigen Challenge J. Immunol., January 1, 2005; 174(1): 143 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Keino, T. Kezuka, M. Takeuchi, N. Yamakawa, T. Hattori, and M. Usui Prevention of Experimental Autoimmune Uveoretinitis by Vasoactive Intestinal Peptide Arch Ophthalmol, August 1, 2004; 122(8): 1179 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kezuka, M. Takeuchi, H. Keino, Y. Usui, A. Takeuchi, N. Yamakawa, and M. Usui Peritoneal Exudate Cells Treated with Calcitonin Gene-Related Peptide Suppress Murine Experimental Autoimmune Uveoretinitis via IL-10 J. Immunol., July 15, 2004; 173(2): 1454 - 1462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Avichezer, R. S. Grajewski, C.-C. Chan, M. J. Mattapallil, P. B. Silver, J. A. Raber, G. I. Liou, B. Wiggert, G. M. Lewis, L. A. Donoso, et al. An Immunologically Privileged Retinal Antigen Elicits Tolerance: Major Role for Central Selection Mechanisms J. Exp. Med., December 1, 2003; 198(11): 1665 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-H. Sonoda, Y. Sasa, H. Qiao, C. Tsutsumi, T. Hisatomi, S. Komiyama, T. Kubota, T. Sakamoto, Y.-I. Kawano, and T. Ishibashi Immunoregulatory Role of Ocular Macrophages: The Macrophages Produce RANTES to Suppress Experimental Autoimmune Uveitis J. Immunol., September 1, 2003; 171(5): 2652 - 2659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Taylor and D. G. Yee Somatostatin Is an Immunosuppressive Factor in Aqueous Humor Invest. Ophthalmol. Vis. Sci., June 1, 2003; 44(6): 2644 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kitaichi, S. Kotake, T. Morohashi, K. Onoe, S. Ohno, and A. W. Taylor Diminution of experimental autoimmune uveoretinitis (EAU) in mice depleted of NK cells J. Leukoc. Biol., December 1, 2002; 72(6): 1117 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Broderick, R. M. Hoek, J. V. Forrester, J. Liversidge, J. D. Sedgwick, and A. D. Dick Constitutive Retinal CD200 Expression Regulates Resident Microglia and Activation State of Inflammatory Cells during Experimental Autoimmune Uveoretinitis Am. J. Pathol., November 1, 2002; 161(5): 1669 - 1677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Dick, C. Broderick, J. V. Forrester, and G. J. Wright Distribution of OX2 Antigen and OX2 Receptor within Retina Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 170 - 176. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
CPM ± SE from
triplicate cultures for each peptide concentration tested.
(B) Average scores and incidence of EAU in C57BL/6 mice
immunized with the native or the truncated peptide (300 µg/mouse).