CD8+ T Cells Play Disparate Roles in the Induction and the Effector Phases of Murine Experimental Allergic Conjunctivitis

Abstract

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 CD8α‐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.

Regulatory T Cells Participate in 4-1BB-Mediated Suppression of Experimental Allergic Conjunctivitis

“…We have previously shown that CD8+ T cells participate in the development of EC during the induction phase [13]. It could be considered that anti-4-1BB Ab treatment affects the number of CD8+ T cells which participate in the development of EC.…”

Functional Foxp3+CD4+CD25(Bright+)“Natural” Regulatory T Cells Are Abundant in Rabbit Conjunctiva and Suppress Virus-Specific CD4+and CD8+Effector T Cells during Ocular Herpes Infection

“…Instead of the common laboratory species, mice, rats, and guinea pigs, we elected to use rabbits as the working animal model, bearing in mind that (i) numerous similarities between rabbit and human OMIS exist (13,66,67); (ii) several T-cell-mediated ocular surface diseases, including herpetic conjunctivitis and recurrent corneal herpetic stromal keratitis (HSK), have been reported to be similar in rabbits and humans, making it the most relevant animal model for exploring these human eye disorders (53,55,80); (iii) compared to mice and rats, rabbit CALT more closely resembles human CALT (23,25,28,44); (iv) microanatomy and immunohistological studies indicate that rabbit conjunctival mucosa is comparable to that of humans and has a typical follicular ultrastructure with an abundance of "conjunctival lymphoid follicles," whereas no lymphoid tissue was identified in mice and rats (28,42,43,47,84); (v) from a practical standpoint, unlike mice, rats, and guinea pigs, rabbits possess a relatively large conjunctival surface, offering abundant mucosa-associated lymphoid tissue for in vitro studies; and (vi) the recent availability of many monoclonal and polyclonal antibodies specific to rabbit immune cell CD markers, cytokines, and growth factors provide useful immunological tools for an unprecedented phenotypic and functional analysis of rabbit T-cell repertoire and function.…”

Classification of ocular allergy

“…A recent study suggests that CD8 þ T cells promote the development of experimental allergic conjunctivitis in the induction phase, indicated by reduced conjunctival eosinophilic infiltration in ragweed-immunized/challenged CD8-deficient mice compared with wild type mice [21]. Another study found that thymus-derived CD4 þ CD25 þ T cells suppress the development of experimental allergic conjunctivitis in mice sensitized/challenged with short ragweed [22 ].…”