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HJ Kaplan, Z Wang, N Bora, J Sohn, J Cruz, H Shao, TJ McCarthy, MJ Welch; MicroPET Imaging in Experimental Autoimmune Anterior Uveitis (EAAU): Dynamic Systemic Traffic of CD4 T Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4375.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To study CD4 T cell trafficking in a model of autoimmunity using in vivo imaging with a microPET scanner and 64Cu labeled anti-CD4 monoclonal antibody. Methods: T cell trafficking was studied by radiolabeling of CD4 T cells with 64CuDOTA anti-CD4 monoclonal antibody. Positron emission tomography was performed using a dedicated small animal imaging tomography machine, the microPET (Concorde, Inc.). The effect of 64CuDOTA anti-CD4 labeling on the function of naïve and sensitized CD4 T cells was studied both in vivo (adoptive transfer of disease) and in vitro (proliferation, activation, apoptosis, adhesion molecule expression). 400-600 uCi 64CuDOTA anti-CD4 was injected intravenously at various time points in Lewis rats immunized with MAA+CFA+PTX in the right foot pad. Twelve hours after injection microPET imaging was performed. 3-D rotational image analysis of the systemic lymphoid system occurred at the onset, peak and resolution of EAAU. 64CuDOTA MOPC was injected in a control panel of recipients with EAAU. Results: Primary lymphoid structures (spleen, liver and bone marrow) were imaged in normal Lewis rats with 64CuDOTA anti-CD4 but not 64CuDOTA MOPC (i.e. the control antibody [Ab]). Prior to the onset of EAAU (day 14) CD4 T cells were imaged in the axillary, para-aortic and inguinal lymph nodes (LNs) with 64CuDOTA anti-CD4 (but not the control Ab). At the peak of EAAU the axillary LNs were still imaged but not the abdominal (i.e. para-aortic and inguinal) LNs. On resolution of EAAU the axillary LNs were no longer imaged but the abdominal LNs were once again visualized. With chronic resolution of EAAU no LNs were imaged. Conclusion: Trafficking of CD4 T cells can be followed in vivo with 64CuDOTA anti-CD4 and microPET imaging. Just prior to the onset of uveitis the regional LNs have an expanded CD4 T cell population. However, there is a dynamic shift in CD4 T cells between the regional and systemic LN populations during the evolution and resolution of intraocular inflammation.
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