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Gene transfer into CD4+ T lymphocytes: Green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses

Nature Medicine volume 5, pages 843–847 (1999)Cite this article

Encephalitogenic T cells can be isolated readily from naive or antigen-primed immune organs and propagated as clonal populations in vitro1. These T-cell lines have helped us to understand better epitope recognition, TCR gene use, cytokine patterns, and T-cell interactions with components of the CNS (ref. 2), and have provided a basis for the design of new strategies to treat autoimmune diseases3,4,5,6.

However, essential steps in the development of autoimmune disease have remained obscure. For example, it is well known that activated, autoaggressive T cells fail to attack the CNS immediately after transfer. The formation of an inflammatory infiltrate and associated tissue damage require a lag phase of at least 3 days. The events that occur during this period, in particular the distribution of the encephalitogenic T-cell population and the properties they assume, are unknown. The subsequent migration patterns of inflammatory cells within the target tissue, and their interaction modes with local brain cells, are also incompletely understood. Finally, most infiltrating T cells are known to undergo apoptotic death in the CNS lesion7, but whether or not some T cells survive and return to the periphery is controversial.

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Figure 1: Retroviral gene vector and expression of GFP in CD4+ T lymphocytes.
Figure 2: TMBPGFP cells in vivo and isolated ex vivo.
Figure 3: TMBPGFP cells in the immune repertoire of Lewis rats.

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Acknowledgements

We thank I. Haarmann, P. Grämmel and D. Büringer for their technical assistance, and M. Bradl and C. Linington for critically reading the manuscript. This work was partly supported by Schering AG, Berlin.

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  1. Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18A, Martinsried, 82152, Germany

    Alexander Flügel, Tomasz Berkowicz & Hartmut Wekerle

  2. Max-Planck-Institute of Biochemistry, Martinsried, Germany

    Michael Willem

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Correspondence to Hartmut Wekerle.

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Flügel, A., Willem, M., Berkowicz, T. et al. Gene transfer into CD4+ T lymphocytes: Green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses. Nat Med 5, 843–847 (1999). https://doi.org/10.1038/10567

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