Naslov
NKG2D stimulation of CD8+ T cells during priming promotes their capacity to produce cytokines in response to viral infection in mice

Autori
Kavazović, Inga ; Lenartić, Maja ; Jelenčić, Vedrana ; Jurković, Slaven ; Lemmermann, NA ; Jonjić, Stipan ; Polić, Bojan ; Wensveen, Felix

Izvornik
European journal of immunology (0014-2980) 47 (2017), 7; 1123-1135

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cytokines ; Dap10 ; Effector CD8+ T cells ; LCMV ; NKG2D ; mCMV

Sažetak
NKG2D is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ and CD8+ T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8+ T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here we studied the impact of NKG2D on effector CD8+ T-cell formation. NKG2D-deficiency that is restricted to murine CD8+ T cells did not impair antigen-specific T-cell expansion following mCMV and LCMV infection, but reduced their capacity to produce cytokines. Upon infection, conventional dendritic cells induce NKG2D ligands, which drive cytokine production on CD8+ T cells via the Dap10 signaling pathway. T-cell development, homing and proliferation were not affected by NKG2D deficiency and cytotoxicity was only impaired when strong T-cell receptor stimuli were used. Transfer of antigen-specific CD8+ T cells demonstrated that NKG2D-deficiency attenuated their capacity to reduce viral loads. The inability of NKG2D-deficient cells to produce cytokines could be overcome with injection of IL-15 super-agonist during priming. In summary, our data shows that NKG2D has a non-redundant role in priming of CD8+ T cells to produce antiviral cytokines. Upon viral infection, classical Dendritic cells induce expression of the NKG2D ligand H60. NKG2D stimulation during priming enhances the ability of CD8 T cells to produce cytokines but not increases cytotoxic potential upon T cell receptor engagement in the periphery.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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