Targeting CD6 for the treatment of experimental autoimmune uveitis

L Zhang, Y Li, W Qiu, BA Bell, N Dvorina… - Journal of …, 2018 - Elsevier
L Zhang, Y Li, W Qiu, BA Bell, N Dvorina, WM Baldwin III, N Singer, T Kern, RR Caspi
Journal of autoimmunity, 2018Elsevier
Objective CD6 is emerging as a new target for treating many pathological conditions in
which T cells are integrally involved, but even the latest data from studies of CD6 gene
engineered mice were still contradictory. To address this issue, we studied experimental
autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6
knockout (KO) mice. Methods After EAU induction in WT and CD6 KO mice, we evaluated
ocular inflammation and compared retinal antigen-specific T-cell responses using scanning …
Objective
CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice.
Methods
After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naļve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies.
Results
In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one of these cross-reactive mAbs significantly ameliorated retinal inflammation in EAU induced by the adoptive transfer of uveitogenic T cells.
Conclusions
Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases.
Elsevier