CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell Responses

By S. Suvas, U. Kumaraguru, C. Pack, Sujin Lee, B. Rouse. Journal of Experimental Medicine, 2003

622 citations recorded by the source corpus.

Naturally occurring CD4+CD25+ regulatory T cells appear important to prevent activation of autoreactive T cells. This article demonstrates that the magnitude of a CD8+ T cell–mediated immune response to an acute viral infection is also subject to control by CD4+CD25+ T regulatory cells (Treg). Accordingly, if natural Treg were depleted with specific anti-CD25 antibody before infection with HSV, the resultant CD8+ T cell response to the immunodominant peptide SSIEFARL was significantly enhanced. This was shown by several in vitro measures of CD8+ T cell reactivity and by assays that directly determine CD8+ T cell function, such as proliferation and cytotoxicity in vivo. The enhanced responsiveness in CD25-depleted animals was between three- and fourfold with the effect evident both in the acute and memory phases of the immune response. Surprisingly, HSV infection resulted in enhanced Treg function with such cells able to suppress CD8+ T cell responses to both viral and unrelated antigens. Our results are discussed both in term of how viral infection might temporarily diminish immunity to other infectious agents and their application to vaccines. Thus, controlling suppressor effects at the time of vaccination could result in more effective immunity.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/2b999b95c46347879b730ff541a95687cee5ac43

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Citations in the corpus

Redefining chronic viral infection. (2009, neutral): “rus infections (Fernandez et al., 2008; Suvas et al., 2003).”
Mechanisms of suppression by suppressor T cells (2005, background): “Interference with suppression in vivo Various immune responses, including those specific for viruse”
Regulatory T cells and infection: a dangerous necessity (2007, background): “In many infections in both mice and humans, depletion of natural T Reg cells (using CD25-specific antibodies) has resulted in enhanced effector immune response”
Natural regulatory T cells in infectious disease (2005, background): “Comparisons of the HSV immune response in natural T reg cell–depleted and intact mice have shown that responses are considerably enhanced in the absence of natural T reg cell”
Molecular Mechanisms of Treg-Mediated T Cell Suppression (2012, background): “A main function of Tregs is suppression of activation and expansion of naïve Tcons, but they can also inhibit activated effector T cells and memory CD4 + (Levings et al., 2001) and CD8 + (Suvas et al., 2003) T cells.”