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Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection.

Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection.
Author Information (click to view)

Malyshkina A, Littwitz-Salomon E, Sutter K, Zelinskyy G, Windmann S, Schimmer S, Paschen A, Streeck H, Hasenkrug KJ, Dittmer U,


Malyshkina A, Littwitz-Salomon E, Sutter K, Zelinskyy G, Windmann S, Schimmer S, Paschen A, Streeck H, Hasenkrug KJ, Dittmer U, (click to view)

Malyshkina A, Littwitz-Salomon E, Sutter K, Zelinskyy G, Windmann S, Schimmer S, Paschen A, Streeck H, Hasenkrug KJ, Dittmer U,

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Scientific reports 2017 08 107(1) 7785 doi 10.1038/s41598-017-08578-7

Abstract

CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection. During chronic FV infection a population of activated FV-specific CD4+ T cells did not express cytotoxic molecules, but Fas Ligand that can induce Fas-induced apoptosis in target cells. Using an MHC II-restricted in vivo CTL assay we demonstrated that FV-specific CD4+ T cells indeed mediated cytotoxic effects against FV epitope peptide loaded targets. CD4 + CTL killing was also detected in FV-infected granzyme B knockout mice confirming that the exocytosis pathway was not involved. However, killing could be blocked by antibodies against FasL, which identified the Fas/FasL pathway as critical cytotoxic mechanism during chronic FV infection. Interestingly, targeting the co-stimulatory receptor CD137 with an agonistic antibody enhanced CD4+ T cell cytotoxicity. This immunotherapy may be an interesting new approach for the treatment of chronic viral infections.

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