Journal of Experimental Medicine, Vol 156, 1842-1847, Copyright © 1982 by Rockefeller University Press

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Selection of restriction specificities of virus-specific cytotoxic T cells in the thymus: no evidence for a crucial role of antigen- presenting cells

RM Zinkernagel

The proposal was tested that (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras expressed predominantly P1-restricted T cells because donor derived stem cells were exposed to recipient derived antigen- presenting cells in the thymus. Because P1 recipient-derived antigen- presenting cells are replaced only slowly after 6-8 wk by (P1 X P2) donor-derived antigen-presenting cells in the thymus and because replenished pools of mature T cells may by then prevent substantial numbers of P2-restricted T cells to be generated, a large portion of thymus cells and mature T cells were eliminated using the following treatments of 12-20-wk-old (P1 X P2) F1 leads to P1 irradiation bone marrow chimeras: (a) cortisone plus antilymphocyte serum, (b) Cytoxan, (c) three doses of sublethal irradiation (300 rad) 2d apart, and (d) lethal irradiation (850 rad) and reconstitution with T cell-depleted (P1 X P2) F1 stem cells. 12-20 wk after this second treatment, (P1 X P2) leads to P1 chimeras were infected with vaccinia-virus. Virus- specific cytotoxic T cell reactivity was expressed by chimeric T cells of (P1 X P[2) F1 origin and was restricted predominantly to P1. Virus- specific cytotoxic T cells, therefore, do not seem to be selected to measurable extent by the immigrating donor-derived antigen-presenting cells in the thymus; their selection depends apparently from the recipient-derived radioresistant thymus cells.
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This article has been cited by other articles:

• Martinic, M. M., Rulicke, T., Althage, A., Odermatt, B., Hochli, M., Lamarre, A., Dumrese, T., Speiser, D. E., Kyburz, D., Hengartner, H., Zinkernagel, R. M. (2003). Efficient T cell repertoire selection in tetraparental chimeric mice independent of thymic epithelial MHC. Proc. Natl. Acad. Sci. USA 100: 1861-1866 [Abstract] [Full Text]  

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