Principal Investigators:

Modulation of anti-retroviral T cell responses by different IFNα subtypes

Type I interferons (IFN), which are immediately induced after infection with viruses or other pathogens, are central for direct antiviral immunity and link innate and adaptive immune responses. Their antiviral role has been intensively studied, whereas their influence on adaptive immune cells, especially T cells, remains elusive. In our project, we want to elucidate the role of IFNα subtypes on CD4⁺ T helper cells and regulatory T cells in vitro using a virus-specific T cell proliferation assay. Therapeutic treatment with recombinant IFNα subtypes during acute and chronic Friend retrovirus (FV) infection of mice will be performed to further characterize their effects on virus-specific CD4⁺ T cell responses, including effector and memory cell responses as well as suppressive Treg responses in vivo. We also want to analyze the modulation of HIV- or HBV-specific T cell responses by human IFNα subtypes using in vitro re-stimulated T cells isolated from infected patients.

Publications

Dickow J, Francois S, Kaiserling RL, Drexler I, Westendorf AM, Lang KS, Santiago ML, Dittmer U, Sutter K. Diverse immunomodulatory effects of individual IFNα subtypes on virus-specific CD8+ T cell responses, Front Immunol 2019; 10, 2255.

Braun E, Hotter D, Koepke L, Zech F, Gross R, Sparrer KMJ, Muller JA, Pfaller CK, Heusinger E, Wombacher R, Sutter K, Dittmer U, Winkler M, Simmons G, Jakobsen MR, Conzelmann KK, Pohlmann S, Munch J, Fackler OT, Kirchhoff F, Sauter D. Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. Cell Rep 2019; 27, 2092-104 e10.

Shen F, Li Y, Wang Y, Sozzi V, Revill PA, Liu J, Gao L, Yang G, Lu M, Sutter K, Dittmer U, Chen J, Yuan Z. Hepatitis B virus sensitivity to interferon-alpha in hepatocytes is more associated with cellular interferon response than with viral genotype. Hepatology 2018; 67, 1237-52.

Knuschke T, Rotan O, Bayer W, Kollenda S, Dickow J, Sutter K, Hansen W, Dittmer U, Lang KS, Epple M, Buer J, Westendorf AM. Induction of Type I Interferons by Therapeutic Nanoparticle-Based Vaccination Is Indispensable to Reinforce Cytotoxic CD8(+) T Cell Responses During Chronic Retroviral Infection. Front Immunol 2018; 9, 614.

Song J, Li S, Zhou Y, Liu J, Francois S, Lu M, Yang D, Dittmer U, Sutter K. Different antiviral effects of IFNalpha subtypes in a mouse model of HBV infection. Sci Rep 2017; 7, 334.

Ziegler SM, Beisel C, Sutter K, Griesbeck M, Hildebrandt H, Hagen SH, Dittmer U, Altfeld M. Human pDCs display sex-specific differences in type I interferon subtypes and interferon alpha/beta receptor expression. Eur J Immunol 2017; 47, 251-6.

Li Y, Sun B, Esser S, Jessen H, Streeck H, Widera M, Yang R, Dittmer U, Sutter K. Expression Pattern of Individual IFNA Subtypes in Chronic HIV Infection. J Interferon Cytokine Res 2017; 37, 541-9.

Lavender KJ*, Gibbert K*, Peterson KE, Van Dis E, Francois S, Woods T, Messer RJ, Gawanbacht A, Muller JA, Munch J, Phillips K, Race B, Harper MS, Guo K, Lee EJ, Trilling M, Hengel H, Piehler J, Verheyen J, Wilson CC, Santiago ML, Hasenkrug KJ, Dittmer U. Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo. J Virol 2016; 90, 6001-13.

Harper MS, Guo K, Gibbert K, Lee EJ, Dillon SM, Barrett BS, McCarter MD, Hasenkrug KJ, Dittmer U, Wilson CC, Santiago ML. Interferon-alpha Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms. PLoS pathogens 2015; 11, e1005254.

Littwitz-Salomon E, Akhmetzyanova I, Vallet C, Francois S, Dittmer U, Gibbert K. Activated regulatory T cells suppress effector NK cell responses by an IL-2-mediated mechanism during an acute retroviral infection. Retrovirology 2015; 12, 66.

Xu HC, Grusdat M, Pandyra AA, Polz R, Huang J, Sharma P, Deenen R, Kohrer K, Rahbar R, Diefenbach A, Gibbert K, Lohning M, Hocker L, Waibler Z, Haussinger D, Mak TW, Ohashi PS, Lang KS, Lang PA. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity 2014; 40, 949-60.

Gibbert K, Joedicke JJ, Meryk A, Trilling M, Francois S, Duppach J, Kraft A, Lang KS, Dittmer U. Interferon-alpha Subtype 11 Activates NK Cells and Enables Control of Retroviral Infection. PLoS pathogens 2012; 8, e1002868.

Gibbert K, Dietze KK, Zelinskyy G, Lang KS, Barchet W, Kirschning CJ, Dittmer U. Polyinosinic-polycytidylic acid treatment of Friend retrovirus-infected mice improves functional properties of virus-specific T cells and prevents virus-induced disease. Journal of immunology 2010; 185, 6179-89.

Gerlach N, Gibbert K, Alter C, Nair S, Zelinskyy G, James CM, Dittmer U. Anti-retroviral effects of type I IFN subtypes in vivo. Eur J Immunol 2009; 39, 136-46.