Earlier in the study of ACAID, it was reasoned that mechanisms that mediated suppression of a Th1 response might in fact include a deviation toward a Th2 response. More recently, it has been clearly shown that at least the development of the CD8+ efferent Treg cell is not dependent on a Th2 response . Thus the question arose as to whether the efferent CD8 + Treg cell might suppress Th2 responses, as well as Th1.
Historically, ACAID-APCs are shown to induce suppression of Th1-mediated immune responses. A recent publication by Katagiri et al.  showed that preemptive induction of ACAID could inhibit Th2 responses using a mouse model of ovalbumin (OVA)-induced, Th2-dependent pulmonary inflammation. Injecting OVA alone into the AC or injecting OVA-pulsed, TGF-p2-treated PECs intravenously before sensitization blocked every aspect of Th2 inflammation that included OVA-specific IgE production, Th2 cytokine (IL-4, IL-5, and IL-13) production, and eosinophil and lymphocyte pulmonary infiltration.
Further study showed that ACAID-APCs given to Th2-presensitized mice suppressed most aspects of the Th2 response (i.e. reduced pulmonary inflammatory cell infiltration and Th2 cytokine production) as well as subsequent pathogenesis (i.e. airway hyperresponsiveness and mucus production) . Furthermore, suppression of the presensitized Th2 response is also mediated by CD8 + Treg cells in ACAID. However, there was no suppression of OVA-specific IgE in presensitized mice by ACAID-APC. Since IgE is produced by existing long-lived plasma cells in presensitized mice, the suppression of IgE may be a late phenomenon, one that occurs after the immune traits are recessed. The treatment with ACAID-APCs in both naïve and pre-sensitized mice did not alter interferon-7 production. Thus, ACAID-APC induced tolerance and not merely an induction of a Th1 response capable of suppressing Th2-mediated pathogenesis in a mouse model of human allergic asthma.
Early explanations of ACAID mechanisms suggested that Th1 responses were being modulated by generating a Th2 response. However, several pieces of evidence support ACAID not being a Th2 response. Kosiewicz and Streilein  reported that no Th2 cytokine-producing cells were found in spleen and lymph nodes of mice that only received intracameral inoculation of antigens. Instead, the splenic cells of these mice secreted only TGF-p when stimulated with OVA in vitro. Furthermore, mice deficient in IL-4/IL-13 and STAT6 genes that are critical for Th2 development readily acquired ACAID suppression after intracameral inoculation of antigens . Finally, the ability of ACAID and ACAID-tolerogenic APCs to suppress Th2-mediated pathogenesis adds the additional evidence to put the notion that ACAID is similar to a Th2 response to rest.
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