Anterior chamber-associated immune deviation-inducing cells activate T cells, and rescue them from antigen-induced apoptosis.

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Immune responses to antigens injected into the anterior chamber of the eye are devoid of T helper 1 (Th1)-type responses of the delayed hypersensitivity type, which has been termed anterior chamber-associated immune deviation (ACAID). Recently, it has been found that peritoneal exudate cells (PEC) from normal mice can be made to acquire the capacity to induce ACAID in vivo when the cells are pulsed with antigen in vitro in the presence of transforming growth factor-beta2 (TGF-beta2), a major cytokine in the ocular microenvironment. We now report that when ovalbumin (OVA)-specific T cells from DO11.10 transgenic mice, or from OVA-primed normal mice, were activated in vitro by normal (untreated) PEC pulsed with OVA, the responding T cells were induced to undergo apoptosis. However, when PEC were first treated with TGF-beta2 and then used to stimulate DO11.10 T cells in the presence of OVA, T-cell proliferation occurred without evidence of increased apoptosis. The ability of TGF-beta2 to rescue responding T cells from apoptosis rested with the capacity of this cytokine to inhibit interleukin-12 (IL-12) production by PEC. Untreated PEC produced large amounts of IL-12 upon interaction with responding T cells. Under these conditions, tumour necrosis factor-alpha (TNF-alpha) production was up-regulated, and this cytokine, in turn, triggered apoptosis among T cells stimulated with OVA-pulsed PEC. From these results, we conclude that TGF-beta2-treated APC promote ACAID by rescuing antigen-activated T cells from apoptosis, and by conferring upon these cells the capacity to down-regulate delayed hypersensitivity.