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* Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114; Divisions of
Rheumatology, Immunology, and Allergy, and
Pulmonary and Critical Care, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan
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Abstract |
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14+ NKT (iNKT) cells. The iNKT cell subpopulations are either CD4+ or CD4-CD8- double negative. This report identifies the subpopulation of iNKT cells that is important for induction of the efferent Tr cell. Because MHC class II-/- (class II-/-) mice generate efferent Tr cells following a.c. inoculation, we conclude that conventional CD4+ T cells are not needed for the development of efferent CD8+ T cells. Furthermore, Ab depletion of CD4+ cells in both wild-type mice (remove both conventional and CD4+ NKT cells) and class II-/- mice (remove CD4+ NKT cells) abrogated the generation of Tr cells. We conclude that CD4+ NKT cells, but not the class II molecule or conventional CD4+ T cells, are required for generation of efferent CD8+ Tr cells following Ag introduction into the eye. Understanding the mechanisms that lead to the generation of efferent CD8+ Tr cells may lead to novel immunotherapy for immune inflammatory diseases. |
Introduction |
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The idea of T cell regulation or T suppressor cells arose in the late 1960s and seemed to peak in the 1970s and early 1980s. In both mice and men, suppression was shown in vitro to require interactions between CD8+ cells and CD4+ cells (1, 2, 3). Moreover, it appeared during this time that a CD4+ T cell subset was required for induction of CD8+ T suppressor as well as there being a subset of target for the CD8+ T suppressor (4, 5, 6). Currently, most reports about Tr cells focus on CD4+ Tr cells, and only a few studies explore questions about efferent CD8+ Tr cells (6, 7). Here we address the mechanisms that give rise to the CD8+ Tr cells in an immune privilege model of tolerance induced in the eye, called anterior chamber-associated immune deviation (ACAID) (8).
CD8+ Tr cells that suppress effector Th1 and Th2 cell function are induced following inoculation of Ag into the anterior chamber (a.c.) of the eye (7, 8, 9, 10). Once Ag is introduced in the eye, bone marrow-derived F4/80+ APCs, indigenous to the eye, capture the Ag and travel via the blood to the marginal zone (MZ) of the spleen (11). The eye-derived APCs secrete macrophage inflammatory protein-2 chemokine that attracts NKT cells along the way to the MZ (12). In turn, after stimulation by CD1d expressed by the F4/80+ APCs, NKT cells secrete RANTES that, in turn, recruits more F4/80+ APCs and T cells to the MZ where clusters of cells accumulate (13). CD8+ Tr cells that suppress Th1 and Th2 effector cells appear in the spleen within 7 days of a.c. inoculation and are dependent on the presence of CD1d-restricted invariant NKT (iNKT) cells (14).
NKT cells are a unique subset of T cells that exist in both mice and humans (15, 16, 17). A major subset of NKT cell subsets is restricted by the MHC class I-like molecule CD1d (18, 19, 20), which is known to be expressed on cells of hemopoietic origin (dendritic cells, B cells, T cells, macrophages) and liver (21). CD1d-restricted NKT cells include CD4+ and CD4-CD8- double-negative (DN) subsets and express a heavily biased TCR repertoire, with the majority expressing an invariant V14J281 TCR--chain and V
8.2, V2, or V7 TCR--chains in mice. A similar subpopulation of NKT cells exists in the human and is defined by its invariant V24JQ TCR chain (18, 22, 23, 24). NKT cells are abundant in the bone marrow, thymus, and liver and are also found in spleen and other peripheral lymphoid organs (25, 26, 27).
NKT cells in mice and men are able to produce large amounts of cytokines within minutes of a signal (28). The phenotype of human NKT cell subsets correlates with the production of a unique set of cytokines: CD4+ NKT cells produced both Th1- and Th2-type cytokines and IL-10; DN NKT cells produced only Th1-type cytokines (29, 30). During ACAID induction in the mouse iNKT cells produce IL-10, but not IL-4 (31) and thus may represent a different activation pathway. Here we explore the phenotype of the iNKT cell that is required and the role of conventional CD4+ T cells and MHC class II (class II) in the development of CD8+ Tr cells in ACAID.
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Materials and Methods |
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Eight- to-20-wk-old mice were used in all experiments. The female C57BL/6 (B6) mice used in these experiments were obtained from the Schepens Eye Research Institute vivarium (Boston, MA) or Taconic Farms (Germantown, NY). Female MHC class II-deficient (class II-/-) mice on a B6 background were obtained from The Jackson Laboratory (Bar Harbor, ME). J281-/- breeders were generated at Chiba University (Chiba, Japan) and were backcrossed nine generations to B6 mice (N9); they were a gift from M. Taniguchi (Chiba University Graduate School of Medicine, Chiba, Japan). Mice were housed on a 12-h light, 12-h dark cycle and were provided food and water ad libitum. All animals were treated humanely and in accordance with the guidelines set forth by the Schepens Eye Research Institute Animal Care and Use Committee and National Institute of Health guidelines.
Abs and flow cytometry
Anti-CD4 mAb (GK1.5) was used for depletion of CD4+ cells in vivo. The following Abs were used for flow cytometric analysis: CyChrome 5 (Cy5)-conjugated anti-TCR mAb (H57-597) and FITC- or PE-conjugated anti-CD4 mAb (RM4-4), FITC-conjugated anti-CD8 mAb (Ly-2, clone 53-6.7), and biotin-conjugated anti-NK1.1 mAb (PK136). They were purchased from BD PharMingen (San Diego, CA). PE-conjugated streptavidin was purchased from Jackson ImmunoResearch Laboratories (West Grove, PA). Rat anti-mouse Fc
R II/III mAb (2.4G2 ascites) was used as the Fc block. Splenic NKT cells were analyzed by flow cytometry as previously described on an EPICS XL flow cytometer (Beckman Coulter, Miami, FL).
Preparation of the -galactosylceramide (-GalCer)-loaded CD1d tetrameric complex.
The lyophilized powder of -GalCer was dissolved in 0.5% Tween 20 (J. T. Baker, Sanford, MI) at a concentration of 220 µg/ml by incubation for 24 h at 37°C with agitation, and stored at -20°C. Before use, the Ag was thawed at room temperature, then sonicated for at least 10 min at 37°C. CD1d tetramers were generated using a dimeric fusion protein of murine CD1d-Fc (32). Fluorescent tetramers were prepared from complexes of Alexa 488 dye-labeled protein A (Molecular Probes, Eugene, OR) and the CD1d-Fc fusion protein as previously described (29). CD1d tetramers were loaded with Ag by incubation for 72 h at 37°C with a 4/1 molar ratio of -GalCer dissolved in 0.5% Tween 20 or were mock-treated with an equivalent volume of 0.5% Tween alone as a negative control. The Ag-loaded or mock-treated CD1d tetramers were used for flow cytometric staining as described previously (29).
Depletion of CD4+ cells
To deplete CD4+ cells, 200 µl of anti-CD4 mAb (GK1.5 ascites, diluted 1/4 in PBS) was injected i.p. into mice. The depletion of CD4+ cells was monitored in spleen cells by flow cytometry. Cells were stained with Cy5-conjugated anti-TCR--chain mAb, and FITC-conjugated anti-CD4 mAb (RM4-4). The percentages of the CD4+ population in the total lymphocyte population before and after GK1.5 treatment were 14.1 and 0.18% in wild-type (WT) mice, and 2.16 and 0.05% in class II-/- mice, respectively.
ACAID induction and assay for delayed-type hypersensitivity (DTH)
ACAID was induced as previously described (33). In brief 2 µl of OVA in PBS (25 mg/ml) was inoculated into the a.c. of the eye using a glass needle. One week later mice were immunized s.c. with OVA (100 µg/50 µl in HBSS) emulsified in CFA (50 µl). To test for DTH, OVA-pulsed, thioglycolate-induced peritoneal exudate cells (PECs; 2 x 105/10 µl of HBSS) were inoculated intradermally (i.d.) into the ear pinnae, and ear swelling was measured 24 h later with an engineer’s micrometer (Mitutoyo, Paramus, NJ).
Local adoptive transfer (LAT) assay
Tr cell function was tested in a LAT assay (9). In brief, effector cells were generated in B6 mice immunized s.c. with OVA (100 µg/50 µl of HBSS) and CFA (50 µl). Ten days later, effector T cells from harvested spleen cells were enriched on pan-T cell IMMULAN columns (Biotecx Laboratories, Watford, U.K.). Naive T cells from unmanipulated mice were used as effector cells for the negative control group. Regulator cells were similarly enriched on pan-T cell IMMULAN columns from spleen cells of ACAID mice 7 days after a.c. inoculation of OVA. Stimulator cells were prepared by pulsing thioglycolate-induced PECs (1 x 106/ml) with OVA (5 mg/ml). Effector cells (5 x 105), stimulator cells (2 x 105), and Tr cells (5 x 105) were resuspended in 10 µl of HBSS and inoculated i.d. into the ear pinnae of naive B6 mice. Ear thickness was measured with an engineer’s micrometer at 24 h. Splenic T cells from unmanipulated mice were used as regulatory cells for the positive control. In some experiments OVA-sensitized whole spleen cells were used as effector and stimulator cells. In that case, whole spleen cells (106) and Tr cells (106) were resuspended in 10 µl of HBSS in the presence of OVA (10 mg/ml) and inoculated i.d. into the ear pinnae of naive B6 mice.
Reconstitution of J281-/- mice
To reconstitute J281-/- mice with CD4+ NKT cells, pan-T cell IMMULAN column-enriched spleen T cells from class II-/- mice were stained with FITC-conjugated anti-CD4 mAb, counterstained with anti-FITC MicroBeads (Miltenyi Biotec, Auburn, CA), and applied to a type MS+ positive selection column with MiniMACS (Miltenyi Biotec). Enriched CD4+ cells (2 x 105/mouse) were injected i.v. into J281-/- mice. Twenty-four hours after reconstitution, J281-/- mice were inoculated (a.c.) with OVA (50 µg/2 µl of PBS) to test ACAID induction.
Statistics
Data were analyzed by ANOVA and Scheffé’s test. A value of p 
0.05 was considered significant.
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Results |
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Previously, we showed that CD1d-restricted iNKT cells were necessary for the establishment of ACAID (14). Also, published data established that the Tr cell that suppresses the effector arm of a Th1 response in ACAID is CD8+ (8). It is therefore well established that iNKT cells are required for the production of efferent CD8+ Tr cells. However, it was never established whether the iNKT cells that are responsible for generating CD8+ Tr cells were CD4+ or DN. Whole splenocytes from naive mice or from a.c.-inoculated mice (day 7) were harvested and immunostained with Cy5-conjugated anti-TCR mAb, biotin-conjugated NK1.1 mAb counterstained with streptavidin-PE and either FITC-conjugated anti-CD4 mAb or anti-CD8 mAb (Fig. 1A). Among NK1.1+ TCR+ cells that were increased in the spleens of ACAID mice (14), only the CD4+ population increased significantly (Fig. 1B). Of the NK1.1+ TCR+ cells, 
85% expressed the invariant chain for their TCR. Since we showed previously that the NKT cell required for ACAID expressed the invariant receptor (iNKT), we wanted to confirm that the CD4+ NKT cell that was increased was an iNKT cell (34). Splenocytes were stained with anti-TCR mAb, anti-CD4 mAb, and -GalCer-loaded CDd tetramer (Fig. 2A). Anti-TCR intermediate -GalCer-loaded CD1d tetramer+ cells (Fig. 2A, circle in left panels) were determined as iNKT cells. The number of total iNKT cells increased after a.c. inoculation with OVA. Among the iNKT cell population (Fig. 2A, left panels) there was a significant increase in the number of CD4+ cells, while the CD4- population showed no significant change (Fig. 2B). Thus, we conclude that it is the CD4+ iNKT cells that increase in the spleen following a.c. inoculation.
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Since class II-/- mice lack conventional CD4+ T cells but still have CD4+ NKT cells (35), we tested whether conventional CD4+ T cells were required for the development of Tr cells. Class II-/- or WT mice were inoculated (a.c.) with OVA, but since conventional CD4+ T cells are needed for the expression of a DTH response, the Tr function of enriched T cells from spleens of a.c.-inoculated class II-/- mice was tested in a LAT assay (Fig. 3). The enriched T cells from OVA a.c.-inoculated class II-/- mice suppressed the adoptively transferred DTH response induced in the recipient’s ear (Fig. 3). Thus, even in the absence of both the class II molecule and conventional CD4+ T cells, efferent Tr cells are generated in ACAID.
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To further address the issue of a role for a CD4+ NKT cell population in ACAID development, class II-/- and WT mice were treated with CD4-specific depleting Ab (GK1.5) 1 day before inoculation (a.c.) of OVA. Seven days later, T cells were enriched from cells harvested from the spleens and were tested in the LAT assay for DTH regulatory activity. Enriched T cells from spleens of OVA-inoculated (a.c.) class II-/- mice suppressed the ear swelling induced by the DTH effector cells that were inoculated into the ear pinnae. However, depletion of CD4+ cells from class II-/- or WT mice before a.c. inoculation prevented the development of regulatory activity, i.e., the Tr cell (Fig. 4). Therefore, CD4+, but not CD4-, iNKT cells are required for generation of the efferent Tr cells.
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281-/- mice
Another approach to the question was to determine whether CD4+ iNKT cells were sufficient to reconstitute ACAID in J281-/- mice. J281-/- mice were reconstituted with CD4+ T cells from class II-/- mice 24 h before OVA inoculation (a.c.). One week later, mice were immunized s.c. with OVA (100 µg/50 µl in HBSS) emulsified in CFA (50 µl). OVA-pulsed, thioglycolate-induced PECs (2 x 105/10 µl of HBSS) were inoculated i.d. into the ear pinnae of naive mice, and ear swelling was measured 24 h later (Fig. 5). Because J281-/- mice only lack iNKT cells, we again concluded that CD4+ iNKT cell are required for the generation of efferent Tr cells.
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Discussion |
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To address the question of the phenotype of the iNKT needed for ACAID, we observed that naive class II-/- mice generate efferent Tr cells following a.c. inoculation of Ag, but CD4+ T cell-depleted class II-/- mice did not. Although Cardell et al. (35) reported that there was proportionally fewer iNKT cells in class II-/- mice than in WT mice, we conclude that there are nevertheless sufficient CD4+ iNKT cells in class II-/- mice to support the development of efferent CD8+ Tr cells in ACAID (11). Because iNKT cells must interact with CD1d to generate CD8+ Tr cells, and here we generate regulatory cells in the absence of class II molecules, we conclude, as did Denkers et al. (36), that class II is not required for the recognition of CD1d by the CD4+ iNKT cell. Thus, the question is raised of the role of CD4 (in the absence of its ligand, class II) on the NKT in generating Tr cells. The data suggest that the CD4 molecule receives signals from ligands other than class II. For instance, another natural ligand for CD4 is IL-16, and IL-16 is chemotactic, up-regulates IL-2R and -, prevents apoptosis, and inhibits CD3 signaling (37). Thus, IL-16 or some other unknown CD4 ligand, rather than class II, may be important in the generation of CD8+ Tr cells, and this opens a new area of investigation.
Human iNKT cell subpopulations are heterogeneous with regard to cytokine production. CD4+ NKT cells produce both Th1/Th2 cytokines and IL-10, while DN NKT cells produce Th1 cytokines (29, 30). In contrast, there is little information on mouse CD4+ NKT cells. However, in a recent review by Kronenberg and Gapin (34), they cited as unpublished observations that all GalCer-activated mouse hepatic iNKT cells produced IFN- and IL-4. The iNKT cells in the ACAID tolerance model in the mouse produce little or no Th1 cytokines, but also are poor producers of IL-4. However, they are good producers of IL-10 (31). These data support the idea that the mouse CD4+ iNKT cell population responsible for peripheral tolerance in ACAID produce cytokines that do not fit within a Th1 or Th2 category, but are fashioned to meet their own regulatory function.
There are conflicting results on the requirement for CD4+ T cell help in the generation of CD8+ CTL (4, 5, 38, 39, 40, 41, 42, 43). Although historically CD8+ T suppressor cells required CD4+ T suppressor inducer cells for their generation (4, 5), little is known about T cell help for the development of efferent CD8+ Tr cells in current models of tolerance. Our results show that neither conventional CD4+ cells nor class II is needed for the generation of efferent CD8+ Tr cells. These data raise the possibility that the suppressor-inducer CD4+ T cells required for the generation of the historical T suppressor cells might well have been CD4+ iNKT cells rather than conventional CD4+ T cells.
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Acknowledgments |
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Footnotes |
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2 Current address: Department of Ophthalmology, Kyushu University School of Medicine, Maidashi 3-1-1 Higashi-Ku, Fukuoka 812-8582, Japan.
3 Current address: Loyola University Medical Center, Department of Surgery, Building 110, Room 4221, 2160 South 1st Avenue, Maywood, IL 60153.
4 Address correspondence and reprint requests to Dr. Joan Stein-Streilein, Schepens Eye Research Institute, 20 Staniford Street, Boston, MA 02114. E-mail address: jstein{at}vision.eri.harvard.edu
5 Abbreviations used in this paper: Tr, T regulatory; a.c., anterior chamber; ACAID, anterior chamber-associated immune deviation; class II, MHC class II; Cy5, CyChrome 5; DN, double negative; DTH, delayed-type hypersensitivity; --GalCer, galactosylceramide; i.d., intradermally; LAT, local adoptive transfer; MZ, marginal zone; PEC, peritoneal exudate cell; Te, T effector; WT, wild type.
Received for publication February 7, 2003. Accepted for publication May 28, 2003.
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References |
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24+ CD4-CD8- T cells. J. Exp. Med. 186:109. chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J. Exp. Med. 180:1097.14+ TCR chain in NK1.1+ T cell populations. Int. Immunol. 7:1157.14-J281 rearrangements in NK1+ T cells. Eur. J. Immunol. 27:1576.[Medline]
/+ cells in the liver of mice. J. Exp. Med. 180:699.24 natural killer T cells. J. Exp. Med. 195:637.This article has been cited by other articles:
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H.-H. Lin, D. E. Faunce, M. Stacey, A. Terajewicz, T. Nakamura, J. Zhang-Hoover, M. Kerley, M. L. Mucenski, S. Gordon, and J. Stein-Streilein The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance J. Exp. Med., May 16, 2005; 201(10): 1615 - 1625. [Abstract] [Full Text] [PDF]
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I. W. Nasr, Y. Wang, G. Gao, S. Deng, L. Diggs, D. M. Rothstein, G. Tellides, F. G. Lakkis, and Z. Dai Testicular Immune Privilege Promotes Transplantation Tolerance by Altering the Balance between Memory and Regulatory T Cells J. Immunol., May 15, 2005; 174(10): 6161 - 6168. [Abstract] [Full Text] [PDF]
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K. Roelofs-Haarhuis, X. Wu, and E. Gleichmann Oral Tolerance to Nickel Requires CD4+ Invariant NKT Cells for the Infectious Spread of Tolerance and the Induction of Specific Regulatory T Cells J. Immunol., July 15, 2004; 173(2): 1043 - 1050. [Abstract] [Full Text] [PDF]
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 P. M. Stuart, B. Summers, J. E. Morris, L. A. Morrison, and D. A. Leib CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1 J. Gen. Virol., July 1, 2004; 85(7): 2055 - 2063. [Abstract] [Full Text] [PDF]
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S. Camelo, A. Shanley, A. S. P. Voon, and P. G. McMenamin The Distribution of Antigen in Lymphoid Tissues following Its Injection into the Anterior Chamber of the Rat Eye J. Immunol., May 1, 2004; 172(9): 5388 - 5395. [Abstract] [Full Text] [PDF]
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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]
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J. Stein-Streilein Invariant NKT Cells as Initiators, Licensors, and Facilitators of the Adaptive Immune Response J. Exp. Med., December 15, 2003; 198(12): 1779 - 1783. [Full Text] [PDF]
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, NKT cells from naive mice; 
, NK1.1+ TCR
) in ear swelling (24 h after ear challenge) is shown on the ordinate, and the identity of the cell mixture inoculated into the ear pinnae for each group is indicated below the abscissa. n, number of mice per group. Significant differences (p 
