Molecules Cytokines And Cells Not Needed For Apc Interactions During Tolerance Induction

In addition to learning about mechanisms of tolerance by the molecules that are needed for the induction of a peripheral tolerance response, it is worth knowing the molecules, cytokines, and cells that are not needed for the generation of the CD8+ Tregs.

Since Class II deficient mice are unable to mount a delayed hypersensitivity (DH) response (they lack the classical CD4+ T effector cells), these KO mice had never been tested for the development of ACAID. However, Nakamura used a local adoptive transfer assay to show that indeed, CD8+ Tregs were generated following AC inoculation of antigen. Thus classical CD4+ T cell help is not needed for the generation of ACAID CD8+ Tregs (29).

Early in the study of ocular immunology, suppression of DH was almost synonymous with ACAID. During this time the idea arose that ACAID was a deviation from a Th1 response to a Th2 response (40). But it now is known that after AC inoculation of antigen, not only are Th1 responses suppressed but Th2 inflammatory responses are regulated as well (41-43). To further test the role of Th2 responses in the generation of ACAID, Nakamura and colleagues showed that IL-14, IL-13, and Stat-6 were not needed for the generation of ACAID since all mice deficient in any one of these molecules were perfectly capable of acquiring ACAID and generating CD8+ Tregs after intracameral injection of antigen. These studies put to rest the idea that ACAID was a deviation towards a Th2 response.

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