In vivo application of mAb directed against the γδ TCR does not deplete but generates “invisible” γδ T cells

C Koenecke, V Chennupati, S Schmitz… - European journal of …, 2009 - Wiley Online Library
C Koenecke, V Chennupati, S Schmitz, B Malissen, R Förster, I Prinz
European journal of immunology, 2009Wiley Online Library
Abstract mAb targeting the γδ TCR have been used for γδ T‐cell depletion with varying
success. Although the depletion‐capacity of the anti‐γδ TCR mAb clone GL3 has been
disputed repeatedly, many groups continue to use γδ T‐cell depletion protocols involving
the mAb clone UC7‐13D5 and find significant biological effects. We show here that
treatment with both GL3 and UC7‐13D5 antibodies does not deplete γδ T cells in vivo, but
rather leads to TCR internalization and thereby generates “invisible” γδ T cells. We …
Abstract
mAb targeting the γδ TCR have been used for γδ T‐cell depletion with varying success. Although the depletion‐capacity of the anti‐γδ TCR mAb clone GL3 has been disputed repeatedly, many groups continue to use γδ T‐cell depletion protocols involving the mAb clone UC7‐13D5 and find significant biological effects. We show here that treatment with both GL3 and UC7‐13D5 antibodies does not deplete γδ T cells in vivo, but rather leads to TCR internalization and thereby generates “invisible” γδ T cells. We addressed this issue using anti‐γδ TCR mAb injections into WT mice as well as into reporter TCR delta locus‐histone 2B enhanced GFP knock‐in mice, in which γδ T cells can be detected based on an intrinsic green fluorescence. Importantly, the use of TCR delta locus‐histone 2B enhanced GFP mice provided here for the first time direct evidence that the “depleted” γδ T cells were actually still present. Our results show further that GL3 and UC7‐13D5 mAb are in part cross‐competing for the same epitope. Assessed by activation markers, we observed in vitro and in vivo activation of γδ T cells through mAb. We conclude that γδ T‐cell depletion experiments must be evaluated with caution and discuss the implications for future studies on the physiological functions of γδ T cells.
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