A novel depletion technique demonstrates that iNKT cells are required throughout CTL cross-priming and uncovers a delayed feedback inhibition mechanism — ASN Events
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A novel depletion technique demonstrates that iNKT cells are required throughout CTL cross-priming and uncovers a delayed feedback inhibition mechanism (#23)

Christoph Heuser 1 , Christina Courrèges 1 , Christoph A. Thaiss 1 2 , Verena Dykstra 1 3 , Christian Kurts 1
  1. Institute of Experimental Immunology, University of Bonn, Bonn, Germany
  2. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
  3. Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany

Cross-priming is essential for the induction of antiviral and antitumor immunity and requires dendritic cells to be licensed by T helper cells or by NKT cells. In classical (i. e. T helper-cell dependent) cross-priming, it is believed that dendritic cells store the licensing information from the helper T cells, so that dendritic cells, T helper cells and cytotoxic T cells (CTL) may hypothetically interact sequentially. The in vivo dynamics of alternative (i.e. NKT-cell mediated) cross-priming are unknown. Using a novel approach to conditionally deplete invariant NKT (iNKT) cells in vivo, we investigated the sequence of cellular interactions. We found that the proliferation of CTL was reduced when iNKT cells were absent during the priming phase of CTL, yet this was compensated by an increase in cytotoxicity on a per-cell basis. Depletion of iNKT cells after the priming of CTL through DCs, surprisingly, led to a much greater expansion of CTL as compared to control mice and hence an improved primary immune response. The differentiation of CTL towards a KLRG1+CD127- SLEC phenotype correlated with the duration and number of iNKT cells present, whereas the frequency of memory precursor CTL was not affected by either parameter.

These data suggest that optimal iNKT-cell induced priming of CTL requires the simultaneous presence of both cell types. Subsequently, inhibitory effects of iNKT cells appear to become dominant, hence limiting CTL expansion.

  1. Kurts, C., Robinson, B. W. S., & Knolle, P. A. (2010). Cross-priming in health and disease. Nature Reviews Immunology, 10(6), 403–14. doi:10.1038/nri2780
  2. Ridge, J. P., Di Rosa, F., & Matzinger, P. (1998). A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature, 393(6684), 474–8. doi:10.1038/30989
  3. Semmling, V., Lukacs-Kornek, V., Thaiss, C. A., Quast, T., Hochheiser, K., Panzer, U., … Kurts, C. (2010). Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs. Nature Immunology, 11(4), 313–20. doi:10.1038/ni.1848