CD4+ T cells develop antiretroviral cytotoxic activity in the absence of regulatory T cells and CD8+ T cells

J Virol. 2013 Jun;87(11):6306-13. doi: 10.1128/JVI.00432-13. Epub 2013 Mar 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytokines / immunology
  • Female
  • Friend murine leukemia virus / immunology*
  • Friend murine leukemia virus / physiology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Retroviridae Infections / immunology*
  • Retroviridae Infections / virology
  • T-Lymphocytes, Regulatory / immunology*


  • Cytokines
  • Histocompatibility Antigens Class II