Histological and clinical study of eyes with true exfoliation and a double-ring sign on the anterior lens capsule.

OBJECTIVE: To investigate the histological and clinical relation between eyes with true exfoliation (TEX) and a double-ring sign (DRS). STUDY DESIGN: Retrospective clinical case study. PARTICIPANTS: Twenty-four eyes of 22 patients who underwent cataract surgery at Kochi Medical School Hospital and its affiliated hospitals during the period from April 1994 to September 2007. METHODS: Twenty-four anterior lens capsules excised in cataract surgery underwent a histological examination and their clinical backgrounds were investigated. The TEX group consisted of 13 eyes with capsular delamination on the anterior lens capsule confirmed by slit-lamp microscopy before the surgery, and the DRS group consisted of 11 eyes that showed a double-ring sign during capsulorrhexis. RESULTS: Twenty-two eyes underwent phacoemulsification and aspiration after uneventful capsulorrhexis. Two eyes that showed phacodonesis underwent extracapsular cataract extraction. In all specimens the capsular delamination was confirmed. In some specimens from both groups, vesicle spaces were observed in the capsule and the underlying epithelium. In the TEX group, 8 eyes had capsular complications, such as pseudoexfoliation and phacodonesis, and in the DRS group, 2 eyes had phacodonesis (p = 0.016, student's t test). CONCLUSIONS: In spite of different clinical processes leading to capsular delamination, there were not any specific histological differences distinguishing the TEX group from the DRS group. The incidence of capsular complications was significantly higher in the TEX group than in the DRS group.

Treatment with FTY720 during the induction or effector phase suppresses the development of experimental allergic conjunctivitis in mice.

PURPOSE: To investigate whether experimental allergic conjunctivitis (EC) can be suppressed by treatment with the immunomodulatory drug FTY720, which reduces the recruitment of effector T cells into inflammatory sites. METHODS: BALB/c mice were actively immunized with ragweed (RW) and then injected intraperitoneally with FTY720 on days 0, 2, 4, 6 and 8 (induction phase treatment) followed by challenge on day 10 with RW-containing eye drops. Alternatively, naïve mice that received RW-primed splenocytes were injected intraperitoneally with FTY720 on days 2 and 4 (effector phase treatment) followed by RW challenge on day 4. Twenty-four hours after RW challenge, conjunctivas and spleens were harvested for histology or immunohistochemistry, and flow cytometric analysis or cytokine assays, respectively. RESULTS: FTY720 treatment during the induction phase suppressed the conjunctival infiltration of T cells as well as eosinophils and macrophages. The splenocytes from induction phase-treated mice contained significantly less CD4(+) and CD8(+) T cells and showed significant suppression of Th2 but not Th1 cytokine production. Effector phase treatment with FTY720 suppressed conjunctival eosinophil infiltration. CONCLUSIONS: These data demonstrate that FTY720 treatment during the induction phase decreases the absolute number of CD4(+) and CD8(+) T cells in the spleen and suppresses Th2 cytokine production by splenocytes. This leads to the suppression of EC. FTY720 treatment also suppresses EC when delivered during the effector phase. Thus, FTY720 treatment may be suitable for treating severe forms of vernal keratoconjunctivitis.

Endogenous IL-17 does not play a significant role in the development of experimental murine allergic conjunctivitis.

BACKGROUND: Endogenous IL-17 is needed for the Ag sensitization that results in murine allergic asthma, a Th2-mediated disease. Here, we aimed to investigate the role IL-17 plays in the development of murine experimental allergic conjunctivitis (EC) which is also a Th2-mediated disease. METHODS: To induce EC, wild-type (WT) and IL-17-deficient (IL-17 KO) mice on the BALB/c and C57BL/6 backgrounds were immunized with ragweed (RW) in alum and challenged with RW in eye drops. Alternatively, EC was induced by adoptively transferring RW-primed splenocytes followed by challenge with RW-containing eye drops. Twenty-four hours after the RW challenge, the conjunctivas and spleens were harvested for histological analyses and cytokine assays, respectively. RESULTS: The WT and IL-17 KO mice on both backgrounds did not differ in terms of the severity of actively induced EC, as evaluated by the conjunctival eosinophil infiltration. They also did not differ with regard to the phenotypes of the inflammatory cells infiltrating the conjunctivas, although primed IL-17 KO splenocytes stimulated in vitro with RW extract did produce significantly higher amounts of IL-4, IL-13 and IFN-gamma than WT splenocytes. Reciprocal adoptive transfer experiments also demonstrated that the IL-17 from both the donor splenocytes and the recipient mice is not involved in the development of EC. CONCLUSIONS: Endogenous IL-17 does not appear to play a significant role in the development of EC.

Depletion of thymus-derived CD4+CD25+ T cells abrogates the suppressive effects of alpha-galactosylceramide treatment on experimental allergic conjunctivitis.

BACKGROUND: We showed previously that alpha-galactosylceramide (alpha-GalCer) treatment elevated splenic CD4+CD25+Foxp3+ T-cell numbers and suppressed the development of experimental allergic conjunctivitis (EC). Here, we investigated whether CD4+CD25+Foxp3+ T cells mediate the suppressive effects of alpha-GalCer treatment on EC. METHODS: To deplete CD4+CD25+Foxp3+ T cells, neonatal mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in aluminum hydroxide. Ten days later, the mice were challenged with RW in eye drops and 24 hours later, the conjunctivas and spleens were harvested for histological and flow cytometric analyses, respectively. alpha-GalCer or vehicle was injected 2 hours prior to RW challenge. In addition, alpha-GalCer was injected into thymus-intact EC-developing mice that had not been treated with anti-CD25 Ab. RESULTS: alpha-GalCer treatment significantly suppressed EC in the thymus-intact mice that had not been treated with anti-CD25 Ab. In contrast, alpha-GalCer treatment of thymectomized and anti-CD25 Ab-treated mice did not affect the severity of EC or splenic CD4+CD25+Foxp3+ T-cell numbers. However, alpha-GalCer treatment did significantly increase splenic CD4+CD25+Foxp3+ T-cell numbers in thymectomized mice that had not received anti-CD25 Ab. CONCLUSIONS: alpha-GalCer treatment during the effector phase of EC increased CD4+CD25+Foxp3+ T-cell numbers, which in turn suppressed the development of EC.

Intraocular pressure elevation after intravitreal or posterior sub-Tenon triamcinolone acetonide injection.

BACKGROUND: Despite the benefits of intraocular steroids for the treatment of inflammatory, neovascular, proliferative, and edematous diseases, one of the side effects is raised intraocular pressure (IOP). In this study, we attempted to identify when IOP elevates, peaks, and returns to the preinjection baseline IOP after intravitreal or posterior sub-Tenon administration of triamcinolone acetonide, as well as the factors that might affect IOP. METHODS: Retrospective case review was undertaken of 69 patients (82 eyes), who received either a 4 mg intravitreal (16 eyes) or a 20 mg posterior sub-Tenon (66 eyes) triamcinolone acetonide injection. IOP assessment for each eye was completed at the preinjection baseline and at the first, third, and sixth month of follow-up. RESULTS: The mean IOP of all eyes increased significantly at each follow-up. The mean maximum elevation ratio from the baseline was 4.0 (SD 5.2) mm Hg. An elevation of 5 mm Hg or greater occurred in 28 eyes (34.1%). The maximum elevation correlated significantly with age (p < 0.01). The incidence of an elevation of 5 mm Hg or greater was significantly higher among patients younger than 60 years (p < 0.01) and relatively higher among female patients (p = 0.051). The mean IOP increased significantly at the first month after intravitreal injection but at all follow-up periods after posterior sub-Tenon injection. There was no significant difference in IOP elevation according to disease type, although eyes with diabetic retinopathy tended to be at higher risk of IOP elevation. Two eyes of two female patients, who had received posterior sub-Tenon injections for the treatment of diabetic retinopathy, required glaucoma surgery. INTERPRETATION: The IOP elevation of 5 mm Hg or greater observed in 34.1% of the eyes was consistent with past reports. IOP elevation was associated with patients of less than 60 years of age and with female sex, and it lasted longer after posterior sub-Tenon injection than after intravitreal injection. Careful assessment of IOP during a follow-up period of at least 6 months is paramount, especially in younger female patients after posterior sub-Tenon injection.

Roles of galectin-9 in the development of experimental allergic conjunctivitis in mice.

BACKGROUND: Galectin-9 was recently identified as a ligand for Tim-3, which negatively regulates Th1 cells. Here, we investigated whether administration of anti-galectin-9 antibodies (Abs) affects the development of murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. METHODS: EC was induced in BALB/c mice by active immunization with ragweed (RW) followed by RW challenge in eye drops. Normal rat IgG (nrIgG) or anti-galectin-9 Ab was injected intraperitoneally into the mice either during the induction phase treatment or effector phase treatment. Alternatively, Abs were injected into the subconjunctival space during the effector phase. To evaluate in vitro effects of anti-galectin-9 Abs, splenocytes from RW-sensitized mice were cultured in vitro with RW in the presence of nrIgG or anti-galectin-9 Abs. To induce EC, these splenocytes were transferred into naïve BALB/c mice followed by RW challenge. RESULTS: Treatment with anti-galectin-9 Abs in vivo during either the induction or effector phase did not significantly affect the severity of EC. However, when the splenocytes from RW-primed mice treated with anti-galectin-9 Abs during the induction phase were stimulated in vitro and adoptively transferred into naïve recipients, they induced significantly severer EC. In contrast, when RW-primed splenocytes were restimulated in vitro with RW in the presence of anti-galectin-9 Abs and then adoptively transferred, they induced less severe EC and produced significantly less IL-5 and IL-13 and more IFN-gamma compared to nrIgG-treated control splenocytes. CONCLUSIONS: These observations may reflect the fact that galectin-9 not only regulates T-cell function, it is also involved in many other biological functions.

B7-H3 regulates the development of experimental allergic conjunctivitis in mice.

B7-H3 negatively regulates Th1-mediated immune responses. Here, we aimed to investigate whether B7-H3 is involved in the development of murine experimental allergic conjunctivitis (EC), which is predominantly mediated by Th2 cells. Intraperitoneal injection of anti-B7-H3 Ab during the induction phase of EC significantly augmented the severity of EC evaluated as conjunctival eosinophil numbers and Ag-induced IL-5 production by splenocytes. Injection of anti-B7-H3 Ab during the effector phase of EC did not significantly affect the severity of EC. In addition, transfer of Ag-primed splenocytes treated with anti-B7-H3 Ab in vitro did not significantly affect the severity of EC, compared to the splenocytes treated with the control Ab. Thus, regulation of EC by blocking of B7-H3 was observed during the induction phase but not the effector phase. Moreover, this study provides a new notion that B7-H3 regulates not only Th1-mediated but also Th2-mediated immune reactions.

Cryptomeria japonica-induced allergic conjunctivitis in mice.

Japanese cedar pollen (Cryptomeria japonica, Cry j) is the most common allergen causing pollinosis in Japan. However, short ragweed pollen is used commonly as the antigen for experimentally-induced allergic conjunctivitis (EC) and Cry j-induced EC in mice has not been published. We actively immunized BALB/c mice with Cry j, and then performed a challenge with eye drops containing Cry j. We evaluated the early phase and late phase reactions in the conjunctiva, using Evans blue dye leakage and eosinophil infiltration, respectively. Significant inhibition of the early phase reaction was observed following pre-challenge with eye drops that block histamine H1 receptor in the conjunctiva. Thus, Cry j-induced EC appears to represent a suitable model for the study of pollinosis in Japan.

[Evaluation of treatment and prognosis of Merkel cell carcinoma of the eyelid in Japan].

PURPOSE: To evaluate retrospectively the management and prognosis of Merkel cell carcinoma of the eyelid in Japanese patients. SUBJECTS AND METHODS: Cases diagnosed as Merkel cell carcinoma of the eyelid from January 1993 to February 2005 in 111 institutions in Japan were included in this retrospective study. Management and prognosis were evaluated. RESULTS: The total number of cases enrolled was 21(5 male and 16 female patients). Excision of the tumor was carried out in 18 cases. Two cases were treated with either irradiation or local injection of interferon after biopsy of the tumor. After initial treatment, there were recurrences in 3 cases; local recurrence in one case and nodal metastasis in two cases. No patient died because of Merkel cell carcinoma of the eyelid. CONCLUSIONS: Excision with wide surgical margins with irradiation is recommended as the first choice of treatment for Merkel cell carcinoma of the eyelid. Because the number of patients was only 21 and the duration of observation was short, further investigation is necessary to determine the optimal management and more accurate prognosis for Merkel cell carcinoma.

Endogenous interleukin-10 produced by antigen-irrelevant cells promotes the development of experimental murine allergic conjunctivitis.

Interleukin (IL)-10 is known to act as an immunoregulatory cytokine in both T helper cell 1 (Th1)- and Th2-mediated immune responses. Here, we ask whether IL-10 regulates the development of experimental allergic conjunctivitis (EC), a Th2-mediated inflammatory disease. Wild-type (WT) and IL-10 knockout (IL-10 KO) mice were immunized with ragweed (RW) and then repeatedly challenged with RW in eye drops. Twenty-four hours after the final challenge, conjunctivas were harvested for histological analysis, while the blood and spleens were used to determine the RW-specific immunoglobulin levels in serum and proliferation or cytokine responses and splenocyte transfer, respectively. The IL-10 KO mice had significantly less severe EC (as determined by conjunctival eosinophil infiltration) than the WT mice and evinced greater RW-specific splenocyte proliferation and cytokine production. However, the RW-specific immunoglobulin levels of the two strains did not differ. When the splenocytes from RW-primed WT mice were transferred into IL-10 KO or WT mice, the IL-10 KO mice showed significantly less conjunctival eosinophil infiltration. In contrast, when the splenocytes from RW-primed IL-10 KO or WT mice were transferred into WT mice, both splenocyte populations generated equivalent severe EC. These data indicate that IL-10 does not serve as an immunoregulatory cytokine in the development of EC. Instead, it appears that IL-10 produced by antigen-irrelevant cells acts in the effector phase to promote the development of EC.

T-cell Ig and mucin domain-containing protein (Tim)-2 regulates murine allergic conjunctivitis during the effector phase.

T-cell Ig and mucin domain-containing protein (Tim)-2 is associated with Th2-dependent immune responses. Here, we investigated whether administration of anti-Tim-2 Abs affects the development of murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. While treatment with anti-Tim-2 Abs in vivo during the induction phase did not affect the severity of EC, treatment during the effector phase augmented EC. The in vitro stimulation of ragweed (RW)-primed splenocytes with RW in the presence of anti-Tim-2 Abs induced significantly more IL-5 and IL-13 production but significantly less IFN-gamma production compared with the control splenocytes treated with normal rat IgG. In addition, the transfer of the anti-Tim-2 Ab-treated splenocytes induced significantly more severe EC than the control splenocytes. Thus, Tim-2 negatively regulates the Th2 differentiation of Ag-primed T-cells and the development of EC during the effector phase.

Long-term survival of a patient with small cell lung cancer associated with cancer-associated retinopathy.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic disorder that is frequently found in patients with small cell lung cancer (SCLC); it is caused by autoantibody to the 23-kDa photoreceptor protein, recoverin. We report a 9-year survivor of SCLC after concurrent chemoradiotherapy. His anti-recoverin antibody remains positive. Long-term survival without SCLC recurrence might be related to an autoimmunity mechanism that causes CAR due to the presence of anti-recoverin antibody cross-reacting with retinal cells and tumor cells. The current literature review was conducted to evaluate the impact on overall survival according to anti-recoverin antibody status.

Thymus-derived CD4+ CD25+ T cells suppress the development of murine allergic conjunctivitis.

CD4+ CD25+ T cells regulate various kinds of immune-mediated diseases. Here, we sought to clarify whether CD4+ CD25+ T cells also regulate the development of experimental allergic conjunctivitis (EC). Thymectomized BALB/c mice, treated with anti-CD25 antibody (PC61), normal rat immunoglobulin G (nrIgG) or left untreated were immunized with short ragweed pollen (RW). Ten days later, the mice were challenged with RW in eye drops, and 24 h later, the conjunctivas, blood and spleens were harvested. The severity of EC, as evaluated by conjunctival eosinophil numbers, was significantly higher in the PC61-treated group as compared with the other two groups. The PC61-treated group also had significantly higher RW-specific IgE and IgG1 levels and displayed RW-specific splenocyte proliferation and RW-induced splenocyte T helper cell 2 cytokine production. However, PC61 treatment of unthymectomized mice did not affect the severity of EC. Thus, thymus-derived CD25+ T cells regulate the development of EC. Furthermore, transfer of Foxp3-expressing CD4+ CD25+ T cells from naïve mice into RW-sensitized mice suppressed the development of EC in these mice after RW challenge. Taken together, these results suggest that CD4+ CD25+ T cells regulate the development of EC.

Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy.

We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.

Vogt-koyanagi-harada disease with onset in elderly patients aged 68 to 89 years.

BACKGROUND: We present the clinical case reports of elderly Vogt-Koyanagi-Harada (VKH) disease patients, including the oldest patient at onset to date. CASES: Four patients with VKH disease, whose ages at onset were 68 to 89 years, were treated at Kochi Medical School Hospital between December 2002 and September 2004. OBSERVATIONS: Four elderly patients were diagnosed with VKH disease according to the International Revised Diagnostic Criteria for VKH disease. Two were treated with corticosteroid pulse therapy, but the other two could not tolerate high-dose steroid therapy and were treated with only topical corticosteroids. All had recurrences, which were treated effectively. None of these patients experienced recurrence after sunset glow fundus was observed in the follow-up period. CONCLUSIONS: VKH disease is thought to be more common in younger people, but it is not as uncommon in elderly people as is generally believed. Among elderly VKH disease patients, some cannot tolerate high-dose corticosteroid therapy, so we need to treat these patients with only topical corticosteroids.

Roles of CD4+CD25+ T cells in the development of experimental murine allergic conjunctivitis.

BACKGROUND: CD25+ regulatory T (T reg) cells play a suppressive role in experimental autoimmune uveoretinitis as well as experimental airway inflammation but their involvement in the development of allergic conjunctivitis (AC) remains unclear. We therefore investigated whether T reg cells play a role in the development of experimental AC (EC). METHODS: BALB/c and C57BL/6 mice were actively immunized with ragweed (RW). The mice were treated with an anti-CD25 Ab (PC61) or control normal rat IgG (nrIgG) either 2 days prior to active immunization or during the induction phase (days 0, 2, 4, 6 and 8). Ten days after active immunization, the mice were challenged with RW-containing drops. Twenty-four hours after the challenge, the conjunctivas were harvested for histological analysis of eosinophil infiltration, and the spleens were harvested for cell culture for splenocyte transfer. Cultured splenocytes were transferred into syngeneic mice, and 4 days after the transfer, the recipient mice were challenged with RW. Twenty-four hours after the challenge, conjunctivas were collected for histological analysis. RESULTS: Pretreatment with PC61 did not affect EC in either strain of mice; however, treatment with PC61 during the induction phase significantly suppressed EC in C57BL/6 mice. In contrast, transfer of RW-primed splenocytes from mice treated with PC61 induced EC that was significantly more severe regardless of strain and treatment protocol. CONCLUSIONS: The finding that T reg cells play a suppressive role in the development of EC in splenocyte transfer experiments suggests that modulation of T reg cells may be a possible therapy for AC.

Antibodies to T-cell Ig and mucin domain-containing proteins (Tim)-1 and -3 suppress the induction and progression of murine allergic conjunctivitis.

The T cell Ig and mucin domain-containing proteins (Tim) regulate Th1- and Th2-mediated immune responses. We investigated the ability of Abs blocking Tim-1 or Tim-3 ligand-binding activity to prevent and treat murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. Treatment with either Ab during the induction phase of EC in actively immunized wild-type mice suppressed EC and upregulated Th1 and Th2 immune responses. In contrast, both Abs exacerbated EC in actively immunized IFN-gamma-knockout mice. Thus, both anti-Tim Abs suppress the pathogenic immune responses generated in the induction phase by upregulating systemic IFN-gamma production. Treatment of actively immunized mice and passively immunized mice with either anti-Tim Ab just prior to RW challenge also suppressed EC. Thus, treatment with anti-Tim-1 or anti-Tim-3 Ab can suppress both the induction and progression of EC, which could indicate potential preventive and/or therapeutic approaches for allergic diseases such as allergic conjunctivitis.

Differential contributions of B7-1 and B7-2 to the development of murine experimental allergic conjunctivitis.

B7-1 and B7-2 are the co-stimulatory molecules that are involved in activation of T cells. We investigated whether B7-1 and B7-2 play a role in the development of T cell-mediated experimental allergic conjunctivitis (EC). EC was induced in Balb/c mice by active immunization with ragweed (RW) followed by RW challenge in eye drops. These mice were treated with neutralizing anti-B7-1 Ab, anti-B7-2 Ab, both Abs, anti-cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) Ab or normal IgGs as controls either during the induction phase or the effector phase. With regard to the induction phase treatment, EC was significantly attenuated when both anti-B7-1 and anti-B7-2 Abs were injected. In contrast, anti-CTLA-4 Ab treatment significantly exacerbated EC. With regard to the effector phase treatment, anti-B7-2 Ab alone significantly attenuated EC, while anti-CTLA-4 Ab tended to exacerbate EC. Collectively, B7-1 and B7-2 differently contribute to the development of EC during the induction and effector phases.

Pharmacokinetic analysis of platelet-activating factor in the tears of guinea pigs with allergic conjunctivitis.

PURPOSE: The aim of this study was to examine the levels of platelet-activating factor (PAF) and lyso-PAF in tears from experimental animals developing allergic conjunctivitis (AC). METHODS: AC was induced in guinea pigs by application of ovalbumin in eye drops. Tear samples were collected from 5 actively sensitized animals and from 5 unsensitized control animals before the challenge, and 1, 2, 4, and 6 h postchallenge. C18:0-PAF, C18:0-lyso-PAF, C16:0-PAF, and C16:0-lyso-PAF levels in the tear samples were determined using liquid chromatography-tandem mass spectrometry. RESULTS: The concentrations of C16:0-PAF, C16:0-lyso-PAF, and C18:0-lyso-PAF were measurable in both unsensitized and sensitized groups, whereas C18:0-PAF was undetectable in tear samples from either group. The levels of C16:0-PAF, C16:0-lyso-PAF, and C18:0-lyso-PAF in sensitized animals increased throughout the time course of the experiment, whereas there was no corresponding increase in the levels of these molecules in the unsensitized group. There were strong correlations between the concentrations of C16:0-PAF and C16:0-lyso-PAF, both in the sensitized and in the unsensitized group, and the concentrations of C16:0-lyso-PAF and C18:0-lyso-PAF within each group. CONCLUSIONS: The data from this study demonstrated that the levels of PAF and lyso-PAF increase in tears in a guinea pig model of AC development and implicate a role for PAF for the development of AC.

CD8+ T cells play disparate roles in the induction and the effector phases of murine experimental allergic conjunctivitis.

Although CD4+ Th2 cells clearly play an essential role in the development of experimental allergic diseases, the functions CD8+ T cells may have in these diseases have been investigated less extensively and remain controversial. Here, we investigated the roles of CD8+ T cells in the development of experimental allergic conjunctivitis (EC). EC was induced in CD8alpha-deficient (CD8KO) mice and wild-type (WT) mice by active immunization with short ragweed pollen (RW) followed by challenge with RW-containing eye drops. Alternatively, EC was induced by transferring RW-primed splenocytes followed by RW challenge. With regard to actively immunized mice, CD8KO mice showed significantly less severe eosinophil infiltration of the conjunctiva and lower total IgE levels, although the levels of the other Igs were equivalent between the two strains. Cytokine production by cultured splenocytes also did not differ, but the WT conjunctivas showed upregulated IL-5 and IL-6 expression and greater upregulation of IL-4 expression than the conjunctivas of CD8KO mice. Thus, CD8+ T cells may play a significant role during the induction phase by aiding IgE production and the generation of Th2 cytokines in the conjunctiva, thus promoting the development of EC. In contrast, splenocytes from CD8KO mice induced significantly more severe EC in WT mice than cells from WT mice. In addition, transfer of RW-primed splenocytes induced significantly more severe eosinophil infiltration in CD8KO recipient mice. Thus, CD8+ T cells promote the development of EC during the induction phase, but suppress it during the effector phase.