CD25+CD4+ Regulatory T Cells from the Peripheral Blood of Asymptomatic HIV-infected Individuals Regulate CD4+ and CD8+ HIV-specific T Cell Immune Responses In Vitro and Are Associated with Favorable Clinical Markers of Disease Status

Abstract

Human immunodeficiency virus (HIV) disease is associated with loss of CD4+ T cells, chronic immune activation, and progressive immune dysfunction. HIV-specific responses, particularly those of CD4+ T cells, become impaired early after infection, before the loss of responses directed against other antigens; the basis for this diminution has not been elucidated fully. The potential role of CD25+CD4+ regulatory T cells (T reg cells), previously shown to inhibit immune responses directed against numerous pathogens, as suppressors of HIV-specific T cell responses was investigated. In the majority of healthy HIV-infected individuals, CD25+CD4+ T cells significantly suppressed cellular proliferation and cytokine production by CD4+ and CD8+ T cells in response to HIV antigens/peptides in vitro; these effects were cell contact dependent and IL-10 and TGF-β independent. Individuals with strong HIV-specific CD25+ T reg cell function in vitro had significantly lower levels of plasma viremia and higher CD4+: CD8+ T cell ratios than did those individuals in whom this activity could not be detected. These in vitro data suggest that CD25+CD4+ T reg cells may contribute to the diminution of HIV-specific T cell immune responses in vivo in the early stages of HIV disease.

Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection

“…A functional impairment of CD8 + T cells has also been described in chronic viral infection effecting humans, like human immunodeficiency virus (HIV) and hepatitis C virus (HCV) [35][36][37][38][39][40][41]. In addition, in both HIV and HCV infection CD4 + Treg have been reported to suppress antiviral T cell responses [1,[42][43][44][45]. Thus, manipulation of Treg functions could be a new therapeutic approach in chronic HIV and HCV infection.…”

Laboratorial atopy markers in children with human immunodeficiency virus

“…In the initial phase, higher Treg activity induces a paradoxical effect of stabilized CD4 + levels by reducing CD8 + T activity (Kinter et al 2004, Eggena et al 2005. Therefore, the progressive reduction in Tregs results in an increased Th2 CD4 + T lymphocyte response to environmental allergens.…”

“…Recently, this contradictory effect has been attributed to functional and quantitative alterations in regulatory T cells (Kinter et al 2004, Eggena et al 2005). These observations suggest that immunological alterations secondary to HIV infection alter the normal allergy control mechanisms, thus permitting an increase in the clinical expression of allergic diseases (Bacot et al 1997).…”

Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian–human immunodeficiency virus strain 89.6p-infected macaques

“…In contrast, expression of CD25 and CD69 on CD4 + T cells was relatively stable (Fig. 3a and not shown).In almost all animals, a CD25 hi -expressing subset could be discriminated, which has been described to represent regulatory T cells (Kinter et al, 2004). Separate analysis revealed that 20-40 % of the total CD25 population belonged to the CD25 hi subset.…”

“…Recently, both events were found to be associated with the development of high virus load in SIVinfected macaques (Sun et al, 2007). Besides a possible direct immunosuppressive effect exerted by several HIV proteins (Cefai et al, 1992;Schindler et al, 2006;Westendorp et al, 1995), the formation of regulatory T cells, specifically the thymus-derived CD25 hi /FOXP3 + /CD152 + subset (Andersson et al, 2005;Estes et al, 2006;Hryniewicz et al, 2006;Kinter et al, 2004;Leng et al, 2002;Nilsson et al, 2006;Tsunemi et al, 2005), was found to be increased in HIV as well as in SIV infection, and was shown to contribute to suppression of HIV-specific immune responses (Kinter et al, 2004;Nilsson et al, 2006;Tsunemi et al, 2005).On the other hand, HIV infection induces a state of chronic immune activation, as shown by increased expression of activation and proliferation markers and increased sensitivity to spontaneous and activationmediated apoptosis induction (Carbone et al, 2000;Gougeon et al, 1993; Hazenberg et al, 2003;Meyaard et al, 1992;Miedema et al, 1988;Ribeiro et al, 2002). Chronic immune activation has been hypothesized Hazenberg et al, 2003; Sousa et al., 2002).…”