Tissue-Specific Abundance of Regulatory T Cells Correlates with CD8+ T Cell Dysfunction and Chronic Retrovirus Loads
- 1 August 2009
- journal article
- Published by The American Association of Immunologists
- Vol. 183 (3), 1636-1643
- https://doi.org/10.4049/jimmunol.0900350
Abstract
Infection of mice with Friend virus induces the activation of CD4+ regulatory T cells (Tregs) that suppress virus-specific CD8+ T cells. This suppression leads to incomplete virus clearance and the establishment of virus persistence. We now show that Treg-mediated suppression of CD8+ T cells is tissue specific, occurring in the spleen but not the liver. Regardless of infection status, there was a 5-fold lower proportion of Tregs in the liver than in the spleen, much lower absolute cell numbers, and the relatively few Tregs present expressed less CD25. Results indicated that reduced expression of CD25 on liver Tregs was due to microenvironmental factors including low levels of IL-2 production by CD4+ Th cells in that tissue. Low CD25 expression on liver Tregs did not impair their ability to suppress CD8+ T cells in vitro. Correlating with the decreased proportion of Tregs in the liver was a significantly increased proportion of virus-specific CD8+ T cells compared with the spleen. The virus-specific CD8+ T cells from the liver did not appear suppressed given that they produced both IFN-γ and granzyme B, and they also showed evidence of recent cytolytic activity (CD107a+). The functional phenotype of the virus-specific CD8+ T cells correlated with a 10-fold reduction of chronic Friend virus levels in the liver compared with the spleen. Thus, suppression of CD8+ T cells by virus-induced Tregs occurs in a tissue-specific manner and correlates with profound effects on localized levels of chronic infection.Keywords
This publication has 41 references indexed in Scilit:
- FoxP3 in Peripheral Blood Is Associated With Operational Tolerance in Liver Transplant Patients During Immunosuppression WithdrawalTransplantation, 2008
- Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cellsNature, 2006
- CD8+T-Cell Dysfunction due to Cytolytic Granule Deficiency in Persistent Friend Retrovirus InfectionJournal of Virology, 2005
- Regulatory T cells: friend or foe in immunity to infection?Nature Reviews Immunology, 2004
- In vivo distribution of receptor for ecotropic murine leukemia virus and binding of envelope protein of Friend Murine leukemia virusArchiv für die gesamte Virusforschung, 2003
- Control of Regulatory T Cell Development by the Transcription Factor Foxp3Science, 2003
- CD4+T Cells and Gamma Interferon in the Long-Term Control of Persistent Friend Retrovirus InfectionJournal of Virology, 2001
- Host Genetic Control of Spontaneous and Induced Immunity to Friend Murine Retrovirus InfectionAnnual Review of Immunology, 1990
- THE MULTI-SUBUNIT INTERLEUKIN-2 RECEPTORAnnual Review of Biochemistry, 1989
- A cell-surface molecule involved in organ-specific homing of lymphocytesNature, 1983