Establishment of stable CD8+ suppressor T cell clones and the analysis of their suppressive function

Hu, Fei-yue; Asano, Yoshihiro; Sano, Kazuya; Inoue, Tadahiro; Furutani-Seiki, Makoto; Tada, Takeshi

doi:10.1016/0022-1759(92)90095-b

Cited by 10 publications

(2 citation statements)

References 42 publications

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“…ϩ T cells with regulatory properties have also been described (71)(72)(73)(74)(75). However, the role of IL-10-producing CD8 ϩ T cells in modulating HIV-specific T cell responses has not been previously addressed.…”

Section: Discussionmentioning

confidence: 99%

HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis

Elrefaei

Barugahare

Ssali

et al. 2006

The Journal of Immunology

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IL-10-producing T cells have been shown to inhibit Ag-specific CD8+ T cell responses, and may play a role in the immune dysregulation observed in HIV-1 infection. We characterized the Gag-specific IL-10 responses by CD8+ T cells in HIV-1-positive volunteers from Uganda. HIV-specific IL-10 responses were detected in 32 of 61 (52.4%) antiretroviral naive and 2 of 15 (13.3%) volunteers with a complete virologic response on antiretroviral therapy (< 400 copies/ml). The frequency of HIV-specific IL-10-positive cells was significantly higher in volunteers with advanced disease (CD4+ T cell count <200 cells/mm3; p = 0.0004), and correlated positively with plasma HIV RNA (r = 0.43, p = 0.0004). Interestingly, the frequency of Gag-specific CD107a/b-, but not IFN-γ-, positive cells was significantly lower in individuals with detectable IL-10-positive CD8+ T cells (p = 0.004). Gag-specific IL-10-positive CD8+ T cells demonstrated a pattern of surface memory marker expression that is distinct compared with CD107a/b- and IFN-γ-positive CD8+ T cell populations (p < 0.0001). Our study describes a distinct population of IL-10-positive CD8+ T cells that may play a role in HIV-associated immune dysfunction.

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Section: Discussionmentioning

confidence: 99%

HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis

Elrefaei

Barugahare

Ssali

et al. 2006

The Journal of Immunology

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“…CD8 T cells may mediate antigen-specific immunosuppression by killing CD4 T helper cells (11,12) or antigen presenting cells (13), or by noncytolytic pathways that have not been clearly defined. Although a number of noncytolytic CD8 T cell clones with inhibitory activity have been described (14)(15)(16)(17), the nature of the primary CD8 T suppressor cells and the mechanism underlying their generation still remain elusive (18)(19)(20). Dendritic cells (DC) * were shown to induce Th1 versus Th2 differentiation depending on their maturation stage, the type and duration of activation, and DC subsets (21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells

Gilliet

Liu

2002

The Journal of Experimental Medicine

577

379

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Although CD8 T cell–mediated immunosuppression has been a well-known phenomenon during the last three decades, the nature of primary CD8 T suppressor cells and the mechanism underlying their generation remain enigmatic. We demonstrated that naive CD8 T cells primed with allogeneic CD40 ligand–activated plasmacytoid dendritic cells (DC)2 differentiated into CD8 T cells that displayed poor secondary proliferative and cytolytic responses. By contrast, naive CD8 T cells primed with allogeneic CD40 ligand–activated monocyte-derived DCs (DC1) differentiated into CD8 T cells, which proliferated to secondary stimulation and killed allogeneic target cells. Unlike DC1-primed CD8 T cells that produced large amounts of interferon (IFN)-γ upon restimulation, DC2-primed CD8 T cells produced significant amounts of interleukin (IL)-10, low IFN-γ, and no IL-4, IL-5, nor transforming growth factor (TGF)-β. The addition of anti–IL-10–neutralizing monoclonal antibodies during DC2 and CD8 T cell coculture, completely blocked the generation of IL-10–producing anergic CD8 T cells. IL-10–producing CD8 T cells strongly inhibit the allospecific proliferation of naive CD8 T cells to monocytes, and mature and immature DCs. This inhibition was mediated by IL-10, but not by TGF-β. IL-10–producing CD8 T cells could inhibit the bystander proliferation of naive CD8 T cells, provided that they were restimulated nearby to produce IL-10. IL-10–producing CD8 T cells could not inhibit the proliferation of DC1-preactivated effector T cells. This study demonstrates that IL-10–producing CD8 T cells are regulatory T cells, which provides a cellular basis for the phenomenon of CD8 T cell–mediated immunosuppression and suggests a role for plasmacytoid DC2 in immunological tolerance.

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Lymphocyte subsets and T h 1/T h 2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome

Sandick

Boermeester

Gisbertz

et al. 2003

Cancer Immunol Immunother

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Establishment of stable CD8+ suppressor T cell clones and the analysis of their suppressive function

Cited by 10 publications

References 42 publications

HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis

HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis

Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells

Lymphocyte subsets and T h 1/T h 2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome

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