title: CD4+ T cells develop antiretroviral cytotoxic activity in the absence of regulatory T cells and CD8+ T cells.
abstract: Conventional CD4(+) T cells play an important role in viral immunity. In most virus infections, they provide essential help for antiviral B and T cell responses. In chronic infections, including HIV infection, an expansion of regulatory T cells (Tregs) has been demonstrated, which can suppress virus-specific CD4(+) T cell responses in vitro. However, the suppressive activity of Tregs on effector CD4(+) T cells in retroviral infection is less well documented in vivo. We took advantage of a transgenic mouse in which Tregs can be selectively depleted to determine the influence of such cells on retrovirus-specific CD4(+) T cell responses during an ongoing infection. Mice were infected with Friend retrovirus (FV), and Tregs were depleted during the acute phase of the infection. In nondepleted mice, activated CD4(+) T cells produced Th1-type cytokines but did not exhibit any antiviral cytotoxicity as determined in a major histocompatibility complex (MHC) class II-restricted in vivo cytotoxic T lymphocyte (CTL) assay. Depletion of Tregs significantly increased the numbers of virus-specific CD4(+) T cells and improved their cytokine production, whereas it induced only very little CD4(+) T cell cytotoxicity. However, after dual depletion of Tregs and CD8(+) T cells, conventional CD4(+) T cells developed significant cytotoxic activity against FV epitope-labeled target cells in vivo and contributed to the control of virus replication. Thus, both Tregs and CD8(+) T cells influence the cytotoxic activity of conventional CD4(+) T cells during an acute retroviral infection.
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Manzke
authors.forename: Ilseyar
authors.initials: I
authors.lastname: Akhmetzyanova
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
authors.forename: Mirko
authors.initials: M
authors.lastname: Trilling
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Zelinskyy
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II
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