CD4+CD25+ Regulatory T Cells in Viral Infections

  • Wayne A. Tompkins
  • Mary B. Tompkins
  • Angela M. Mexas
  • Jonathan E. Fogle


CD4+CD25+Tregulatory (Treg) cells are a thymus-derived distinct lineage of T cells that recognize and suppress the expansion and function of potential self-reactive T cell clones, thus maintaining peripheral self-tolerance. It is now established that Treg cells activated in the peripheral immune compartment also modulate immune responses to pathogens. Data suggest that pathogen activated Treg cells in lymph nodes (LN) down-regulate T and B cells responding to the same pathogen, thus minimizing the immunopathology associated with primary immune responses. While Treg cells normally return to a resting state after elimination of the pathogen, in those infections that are not resolved by an anti-viral immune response, they remain chronically activated and immunosuppressive, thereby contributing to a persistent viremia. It is well-established that chronic Hepatitis B and C infections, as opposed to resolved infections, are associated with an increased number or increased activation state of Treg cells that suppress anti-viral CD4+ and CD8+ T cells and contribute to the long-term viremia. In murine models of HSV-1 infection, in vivo depletion of CD25+ Treg cells in mice results in enhanced anti-HSV CD8+ immune responses and more rapid clearance of virus. Similarly, the CD4+ and CD8+ immune deficiency observed in chronic AIDS lentivirus infections have been attributed to immunosuppressive Treg cells capable of suppressing virus-specific CD4+ and CD8+ cytokine and proliferation responses. Whether these activated Treg cells contribute to the host’s failure to eliminate these lentiviruses is not known. However, it has been demonstrated that virus-specific Tcells are anergic, cannot produce IL2, and cannot expand in response to virus peptide stimulation. Activated CD4+CD25+ Treg cells mediate T cell immunosuppression by contact-dependent mechanisms that transduce a signal for transcriptional down-regulation of cytokine genes, including IL2, and induction of T cell anergy. Recent data suggest that Treg-induced T cell anergy is mediated through the TGF-β/TGF-βR signaling pathway. It is clear from the studies described herein that chronic viral infections are characterized by an early and sustained activation of immunosuppressive CD4+CD25+ Treg cells capable of inhibiting anti-viral CD4+ and CD8+ immune responses, which allows for the establishment of long-term infection.


Treg Cell Suppressor Function Cell Immune Response Activate Treg Cell Treg Suppressor Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Wayne A. Tompkins
    • 1
  • Mary B. Tompkins
  • Angela M. Mexas
  • Jonathan E. Fogle
  1. 1.Immunology ProgramNorth Carolina State UniversityRaleighUSA

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