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J. Y. Niederkorn, P. W. Chen, C. Stevens, J. Mellon, E. Mayhew; Allergic Asthma Exacerbates Corneal Allograft Rejection Mediated by a Mixed Th1 and Th2 Alloimmune Response. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3869.
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We have demonstrated that allergic asthma exacerbates corneal allograft rejection. We wished to determine if this rejection was Th1-based, Th2-based, or a combination of these and if allergic asthma enhanced alloimmune responses.
Airway hyperreactivity (AHR) was induced in BALB/c mice with ovalbumin (OVA) or short ragweed extract (SRW) prior to C57BL/B6 corneal transplantation. Mixed lymphocyte responses (MLR), cytotoxic lymphocyte (CTL), and delayed-type hypersensitivity (DTH) alloimmune responses were examined following graft rejection. MLR supernatants and bronchoalveolar lavage fluid (BALF) were examined for Th1 and Th2 cytokines by ELISA. Th1 (Tim3+) and Th2 (T1/ST2+) CD4+ T cells were isolated from corneal graft rejector mice and adoptively transferred to nude mice, which then received C57BL/6 corneal allografts. Some nude mice received Th2 cells and injections of interferon-<font face="Symbol">g</font> (IFN-<font face="Symbol">g</font>).
AHR mice had an increased tempo and incidence of corneal allograft rejection (P = 0.004), but mounted MLR and DTH responses that were not significantly different from control mice (P>0.05). Moreover, CTL responses were not detected in either AHR mice or control mice. BALF and MLR supernatants from AHR mice had a preponderance of IL-13 and IFN-<font face="Symbol">g</font><font face="Symbol">g</font>. Adoptive transfer studies showed that Th1 and Th2 cells mediated rejection in 40% and 20% of the hosts respectively. However, simultaneous transfer of Th1 and Th2 cells resulted in 100% graft rejection. Moreover, Th2 cells produced 100% corneal graft rejection in hosts that were simultaneously treated with IFN-<font face="Symbol">g</font>.
The results indicate that corneal graft recipients with ongoing AHR mount a mixed alloimmune response that is characterized by production of both Th1 (IFN-<font face="Symbol">g</font><font face="Symbol">g</font>) and Th2 (IL-13) cytokines. Unlike non-atopic hosts, which appear to mediate corneal graft rejection by a Th1-mediated mechanism, atopic hosts reject corneal allografts via a mixed Th1 and Th2 mechanism. IFN-<font face="Symbol">g</font><font face="Symbol">g</font>can substitute for the Th1 component of rejection. Asthma-induced exacerbation of corneal allograft rejection is not due to enhanced MLR, DTH, or CTL alloimmune responses.
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