The toxic effect of radioactive substrate of HSV1-TK on antigen specific T cells during noninvasive imaging

Abstract

Using the ability of genetically modified herpes simplex virus thymidine kinase expressing cells to specifically accumulate radioactively labeled analogs of gancyclovir, we analyzed the distribution of encephalitogenicT cells during prodromal phase of transfer EAE and toxic effect of this accumulation on functional activity ofT cells in vitro and in vivo. Though gamma scanning was not sensitive enough for detection of encephalitogenic T cells in organs with low concentration of them we confirmed that spleen is one of the most important organs forT cells during EAE development. Moreover, we have found a toxic effect of radioactively labeled analogs of GCV on effectorT cells leading to inhibition of proliferation in vitro and significant attenuation of EAE symptoms in vivo. Thus, widely clinically and experimentally applying methods of noninvasive in vivo imaging of adaptive transferred T cells with application of radioactive substrate, as we have shown, can lead to attenuation of functional activity of these cells and accordingly to an inefficiency of therapy or wrong interpretation of the obtained data.

Keywords

Central nervous system / immune system / antigen specific lymphocytes / noninvasive imaging

RIGHTS & PERMISSIONS

Nosov M.A., Anton M., Weber W., Barabanova S.V., Wekerle H., Korneva E.A., Fluegel A.