MicroPET Imaging in Autoimmune Uveitis: Non-Invasive Evaluation of Asymmetric Lymphadenopathy in the Secondary Lymphoid System

Abstract

Abstract: : Purpose: To study CD4+ T cell trafficking in a model of autoimmunity using in vivo imaging with a microPET scanner and novel radio-isotopes. Methods: T cell trafficking was studied by radiolabeling of CD4 T cells with ⁶⁴CuDOTA α-CD4 monoclonal antibody. Positron emission tomography was performed using a dedicated small animal imaging tomography machine, the microPET (Concorde, Inc.). 400-600 µCi ⁶⁴CuDOTA α-CD4 was injected intravenously at various time points in Lewis rats immunized with MAA and adjuvant in the left foot-pad to induce experimental autoimmune anterior uveitis (EAAU). Twelve hours after injection microPET imaging was performed. 3-D rotational image analysis of the primary and secondary lymphoid structures was performed before the onset (day 10), at the onset (day 14), during the peak (day 18) and resolution (day 30) of EAAU. Results: The popliteal, inguinal and iliac lymph nodes (LNs) ipsilateral to the site of sensitization (i.e. on the left, following left foot-pad injection) were increased in size compared to the contralateral side from day 10 and onward. There was a transient increase in size of the para-aortic (day 14 and 30) LNs, which are midline in position, compared to controls. Surprisingly, the ipsilateral (i.e. left) axillary (day 10 and 30) and cardiac (day 18) lymph nodes also showed a transient increase in size, whereas the cervical LNs showed no such asymmetry. The induced anterior uveitis was present in both eyes almost simultaneously although in 10% of rats intraocular inflammation developed in the OS 24 hours before the OD as detected by slit-lamp biomicroscopy. Anatomical studies confirmed the impression provided by microPET scanning. Conclusions: Autoimmune uveitis induced by the injection of MAA in the foot-pad results in a bilateral uveitis. Trafficking of CD4+ T cells in vivo with ⁶⁴CuDOTA α-CD4 and microPET imaging revealed an asymmetric lymphadenopathy ipsilateral to the site of sensitization not only locally (i.e. the popliteal, inguinal and iliac LNs) but at distant remote sites (i.e. the cardiac and axillary LNs). There is a dynamic migration of CD4+ T cells during autoimmune uveitis which appears to result in asymmetric migration of T cells throughout the secondary lymphoid system. The significance of this observation is not known at the present time.

Keywords: autoimmune disease • imaging methods (CT, FA, ICG, MRI, OCT, RTA, S • uveitis-clinical/animal model