期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：16
页码：9226-9230
DOI：10.1073/pnas.151174198
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-{beta} and the cell surface molecule CTLA-4 (CD152). These results suggest a possible explanation for HIV- and human T cell leukemia virus-I-induced immunosuppression in the absence of T cell depletion.
