Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS

Abstract

Due to an error in manuscript preparation, an incorrect shRNA sequence for IRS2 was published. The correct hairpin sequence is a 19-nt stretch beginning from nt 703 of the published IRS2 cDNA sequence (XM_357863). The oligonucleotides cloned into the U6 construct for the IRS2U6 adenovirus are as follows: tcgagGTGACGCTGCAGCTTATGAttcaagagaTCATAAGCTGCAGCGTCACttttt (forward) and ctagAAAAAGTGACGCTGCAGCTTATGAtctcttgaaTCATAAGCTGCAGCGTCACc (reverse). In addition, the shRNA cassettes were cloned into the adenoviral cosmid pAxcwit, which lacks a promoter, and not the cosmid pAxCAwtit, as published..The authors regret this error.

Bystander T cell activation – implications for HIV infection and other diseases

“…Work on the non-pathogenic SIV infections of African green monkeys has revealed an early induction of antiinflammatory molecules, with a distinct profile to that seen in the pathogenic infection of macaques. Early elevated levels of transforming growth factor (TGF)-b are hypothesized to be responsible for the increase in CD25 + T-cell numbers, FOXP3 expression and a later increase in the level of IL-10 [54]. This is consistent with the idea of protective Treg-cell induction early in non-pathogenic infection, although the need for further work to verify the existence of simian counterparts to the human Treg cell has been highlighted.…”

Induction of CD8+ Regulatory T Cells Protects Macaques against SIV Challenge

“…Thus far, the only Tregs that have been proposed to be associated with HIV infection are CD4 + Tregs (CD25 + FoxP3 + CD4 + T cells) that are known to be involved in some models of immune tolerance (Faria and Weiner, 2005); however, their role in HIV infection is not clearly understood. On the one hand, the expansion of CD4 + Tregs has been shown to be associated with the suppression of HIV-specific CD4 + T cell responses and disease progression (Aandahl et al, 2004;Nilsson et al, 2006;Weiss et al, 2004), whereas on the other hand, CD4 + Tregs have been associated with protection from productive infection, CD4 + T cell activation, and disease progression in both humans (Card et al, 2009;Chase et al, 2008;Legrand et al, 2006) and nonhuman primates (Jacquelin et al, 2009;Kornfeld et al, 2005). In the study presented here, the ex vivo removal of CD25 + FoxP3 + CD4 + T cells by a CD25 antibody did not modify either the suppression of CD4 + T cell activation or viral replication.…”

CD8+ regulatory T cells in persistent human viral infections

“…Interestingly, 24 hours after infection a strong induction of TGF-␤ and FoxP3 expression was detected in the blood of infected monkeys that correlated significantly with increased levels of CD8ϩCD25ϩ as well as CD4ϩCD25ϩ T cells [45]. In contrast, the frequency of activated effector T cells and the expression levels of interferon-␥ (IFN-␥) and tumor necrosis factor-␣ rapidly declined to baseline levels after an initial increase [45]. These findings suggest that during primary nonpathogenic SIV infection the generation of FoxP3ϩCD25ϩCD8ϩ T reg cells may play a protective role by suppressing T-cell hyperactivation and the onset of an immune disorder.…”

“…Indeed, the first evidence that CD8ϩ T reg cells might already expand in the acute phase of infection has been forthcoming from a study analyzing primary simian immunodeficiency virus (SIV) infection in African green monkeys [45]. SIV infection is nonpathogenic in African green monkeys and does not induce a progressive immune disorder.…”

“…To determine the mechanisms of protection against SIV in these monkeys, an analysis of T-cell activation status and cytokine expression patterns during primary SIV infection was performed. Interestingly, 24 hours after infection a strong induction of TGF-␤ and FoxP3 expression was detected in the blood of infected monkeys that correlated significantly with increased levels of CD8ϩCD25ϩ as well as CD4ϩCD25ϩ T cells [45]. In contrast, the frequency of activated effector T cells and the expression levels of interferon-␥ (IFN-␥) and tumor necrosis factor-␣ rapidly declined to baseline levels after an initial increase [45].…”