Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection

Michihiro Iwashiro, Ronald J. Messer, Karin E. Peterson, Ingunn M. Stromnes, Tomoharu Sugie, Kim J. Hasenkrug

Research output: Contribution to journalArticlepeer-review

161 Scopus citations


Normal levels of CD4+ regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4+ regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with Friend retrovirus develop approximately twice the normal percentage of splenic CD4+ regulatory T cells and lose their ability to reject certain tumor transplants. The role of CD4+ regulatory T cells was demonstrated by the transmission of immunosuppression to uninfected mice by adoptive transfers of CD4+ T cells. CD4+ T cells from chronically infected mice were also immunosuppressive in vitro, inhibiting the generation of cytolytic T lymphocytes in mixed lymphocyte cultures. Inhibition occurred at the level of blast-cell formation through a mechanism or mechanisms involving transforming growth factor-β and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-l-induced immunosuppression in the absence of T cell depletion.

Original languageEnglish (US)
Pages (from-to)9226-9230
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number16
StatePublished - Jul 31 2001


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