CD8+ T-Cells Suppress Antigen-Specific and Allogeneic CD4+ T-Cell Responses to Herpes Simplex Virus Type 2–Infected Human Dendritic Cells

Abstract

In this study we show that human dendritic cells (DC), productively infected with herpes simplex virus type 2 (HSV-2), activate CD8+ T cells that suppress antigen-specific and alloreactive CD4+ T cell expansion. Addition of CD8+ T cells to cultures of DC and CD4+ T cells blocked CD4+ T-cell proliferation in response to HSV-2-infected but not to uninfected DC. The effect was independent of prior HSV exposure or cognate MHC class I-restricted CD8-DC recognition as it was induced in CD8+ T cells from HSV-2-seronegative individuals and in mixed lymphocyte reactions using allogeneic DC. Both CD8+ CD25+ and CD8+ CD25- cells were shown to have suppressive capacities. The blood-derived CD25+ CD8+ T cells did not express Foxp3 mRNA but had a bona fide antiproliferative capacity in response to both uninfected and HSV-2-infected DC, whereas the CD25-CD8+ T cells were selectively activated to become antiproliferative by HSV-2-infected DC. These data imply that HSV infection of DC could modulate the immune response by activating CD8+ T cells.

FoxP3+CD25+CD8+T-Cell Induction during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques Correlates with Low CD4+T-Cell Activation and High Viral Load

“…These cells had the same phenotypic markers as their CD4 ϩ counterparts and CD8 ϩ regulatory T cells, as previously reported (10,16,33,45,49). The increase in the number of CD8 ϩ CD25 ϩ FoxP3 ϩ T cells during primary infection was correlated with viral load and persisted in two of the three macaques with sustained high plasma viral loads (Ͼ10 5 copies per microliter).…”

“…This suggests that CD8 ϩ CD25 ϩ FoxP3 ϩ T cells are directly or indirectly induced by the presence of virus. Other studies also suggested that CD8 ϩ regulatory T cells are induced during viral infections (36,49), including chronic and advanced HIV infection (22,30). However, FoxP3 expression was not assessed in those studies.…”

“…ϩ CD28 Ϫ regulatory T cells (27,33,45,57), whereas others have described CD8 ϩ CD25 ϩ regulatory T cells (10,16,33,49). Some studies have detected FoxP3 expression in CD8 ϩ regulatory T cells (10,16,33,45).…”

Postimmunization with IFN-γ-Secreting Glioma Cells Combined with the Inducible Nitric Oxide Synthase Inhibitor Mercaptoethylguanidine Prolongs Survival of Rats with Intracerebral Tumors

“…Although MEG treatment did not affect the CD4 ϩ CD25 ϩ Foxp3 ϩ population, we cannot exclude an effect on other populations with suppressive capacity. In this context we observed a reduction of the CD8 ϩ CD25 ϩ , a population reported to include autoreactive T cells capable of inhibiting CD4 ϩ T cells (39,40). In conclusion, this study is the first to show that inhibition of NO using MEG can enhance an IFN-␥-based immunotherapy against experimental i.c.…”

Activation Outcomes Induced in Naïve CD8 T-Cells by Macrophages Primed via “Phagocytic” and Nonphagocytic Pathways

“…The induction in this condition of CD25 and CD69 expression without concomitant full lymphocyte activation (IL-2 production, cell proliferation, etc.) may suggest the generation of regulatory T-cells (Nordstrom et al, 2005;Jarnicki et al, 2006). However, we failed to detect foxp3 expression, a marker of regulatory T-cells, on these CD25ϩ T-cells (Olazabal, I. M., and Sanchez-Madrid, F., unpublished data).…”