Zelinskyy, Gennadiy

Research interests focus on the analysis of the regulation of adaptive antiretroviral (mouse Friend virus (FV)) CD4+ and CD8+ T cell response during acute and chronic infection. Main projects include i) analysis of the expression of inhibitory ligands (PD-L1, PD-L2, CD48, HVEM) on the surface of cells in infected organs ii) interplay between inhibitory ligands, regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSC) on different phases of FV infection iii) the optimization of combined immunotherapies directed at inhibitory mechanisms for the treatment of acute and chronic retroviral infection.

Models available:

  • Friend virus (FV) infection (mouse) provide an excellent model for the characterisation of immune response against acute and chronic retroviral infection.
  • Immune response against influenza virus (mouse).
  • Immune response against Friend virus induced tumor (mouse).

Cells available:

  • Characterisation of the influence of regulatory T cells (Tregs), inhibitory ligands, and myeloid derived supressor cells (MDSCs) on the regulation of virus-specific T cell immune responses.
  • Immunomodulation and experimenthal immunotherapy directed on above mentioned inhibitory factors in order to restore the virus-specific or tumor-specific T cells.

Technology available:

  • Flow cytometry (up to 13-colours).
  • Isolation of different populations of immune cells and in vitro functional characterisation.
  • In vivo and in vitro analysis of immunomodulatory factors directed at antigen-specific T cells.
  • In vivo analysis of antigen-specific cellular cytotoxicity of T cells.

Key publications related to Mye-EUNITER:

  1. Zelinskyy G, Werner T, Dittmer U. Natural regulatory T cells inhibit production of cytotoxic molecules in CD8⁺ T cells during low-level Friend retrovirus infection. Retrovirology. 2013 Oct 24;10:109. doi: 10.1186/1742-4690-10-109.

  2. Dietze KK, Zelinskyy G, Liu J, Kretzmer F, Schimmer S, Dittmer U. Combining regulatory T cell depletion and inhibitory receptor blockade improves reactivation of exhausted virus-specific CD8+ T cells and efficiently reduces chronic retroviral loads. PLoS Pathog. 2013;9(12):e1003798. doi: 10.1371/journal.ppat.1003798.

  3. Zelinskyy G, Myers L, Dietze KK, Gibbert K, Roggendorf M, Liu J, Lu M, Kraft AR, Teichgräber V, Hasenkrug KJ, Dittmer U. Virus-specific CD8+ T cells upregulate programmed death-1 expression during acute Friend retrovirus infection but are highly cytotoxic and control virus replication. J Immunol. 2011 Oct. 1;187(7):3730-7.

  4. Dietze KK, Zelinskyy G, Gibbert K, Schimmer S, Francois S, Myers L, Sparwasser T, Hasenkrug KJ, Dittmer U. Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points. Proc Natl Acad Sci U S A. 2011 Feb. 8;108(6):2420-5.

  5. Zelinskyy G, Dietze KK, Husecken YP, Schimmer S, Nair S, Werner T, Gibbert K, Kershaw O, Gruber AD, Sparwasser T, Dittmer U. The regulatory T cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T cell response. Blood. 8 Oct. 2009, Vol. 114, No. 15, pp. 3199-3207.