Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS - PubMed (original) (raw)
. 2005 Apr;115(4):1082-91.
doi: 10.1172/JCI23006. Epub 2005 Mar 10.
Mickaël J-Y Ploquin, Ivona Pandrea, Abdourahmane Faye, Richard Onanga, Cristian Apetrei, Virginie Poaty-Mavoungou, Pierre Rouquet, Jérôme Estaquier, Lorenzo Mortara, Jean-François Desoutter, Cécile Butor, Roger Le Grand, Pierre Roques, François Simon, Françoise Barré-Sinoussi, Ousmane M Diop, Michaela C Müller-Trutwin
Affiliations
- PMID: 15761496
- PMCID: PMC1062895
- DOI: 10.1172/JCI23006
Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS
Christopher Kornfeld et al. J Clin Invest. 2005 Apr.
Erratum in
- J Clin Invest. 2005 May;115(5):1389
Abstract
T cell activation levels in HIV infection are predictive of AIDS progression. We searched for the immunological correlates of protection against disease progression by studying the early stages of nonpathogenic SIV infection in African green monkeys (SIVagm). The African green monkeys (AGMs) displayed high peak viremias and a transient decline in levels of blood CD4(+) and CD8(+) T cells between days 5 and 17 after infection. A concomitant increase in levels of CD4(+)DR(+), CD8(+)DR(+), and CD8(+)CD28(-) cells was detected. After the third week, T cell activation returned to baseline levels, which suggested a protective downregulation of T cell activation. A very early (24 hours after infection) and strong induction of TGF-beta1 and FoxP3 expression was detected and correlated with increases in levels of CD4(+)CD25(+) and CD8(+)CD25(+) T cells. This was followed by a significant increase in levels of IL-10, whereas IFN-gamma gene upregulation was more transient, and levels of TNF-alpha and MIP-1alpha/beta transcripts did not increase in either blood or tissues. The profiles were significantly different during primary SIV infection in macaques (SIVmac); that is, there was a delayed increase in IL-10 levels accompanied by moderate and persistent increases in TGF-beta levels. Together, our data show that SIVagm infection is associated with an immediate antiinflammatory environment and suggest that TGF-beta may participate in the generation of Tregs, which may prevent an aberrant chronic T cell hyperactivation.
Figures
Figure 1
Plasma viral RNA copy numbers were measured by real-time PCR (cut off value, 103 copies/ml of plasma). (A) Macaques infected with SIVmac251. (B) AGMs infected with SIVagm.sab92018.
Figure 2
CD4+/CD8+ T cell ratio during SIV infection. Data obtained with macaques (A and C) and AGMs (B and D). CD4+/CD8+ T cell ratios during SIV infection were determined in blood (A and B) and in LN (C and D) for 3 SIVagm-infected AGMs (SAB98007, SAB98008, and SAB98011), 2 SIVmac251-infected macaques (MACQ172 and MACQ205), and mock-infected controls (SAB98001, SAB98006, MACN894, and MAC141A). Similar profiles to these shown here were obtained in blood of the 6 other AGMs (SAB97008, SAB98013, SAB00020, SAB01013, SAB01015, and SAB02003) (data not shown). Open and filled symbols represent uninfected and SIV-infected monkeys, respectively.
Figure 3
Frequency of circulating activated T cells during SIV infection. Percentage of HLA-DR+ cells within blood CD4+ T (A and B) and CD8+ T cells (C and D). (A and C) SIVmac-infected macaques. Open and filled symbols represent uninfected and SIV-infected macaques, respectively. (B and D) Bold and thin lines represent the mean from 9 SIVagm-infected AGMs and 2 uninfected AGMs (SAB98001 and SAB98006), respectively.
Figure 4
Expression of β chemokine gene transcripts in blood and tissues of 3 SIVagm-infected AGMs (SAB98007, SAB98008, and SAB98011) (A) and 2 mock-infected AGMs (SAB98001 and SAB98006) (B). Values at time points after SIV inoculation (days 5–180) are expressed as n-fold increases relative to values found before infection (BI). Gene expressions levels are represented by box plots. Gray boxes indicate statistically significant increases (P < 0.05, Wilcoxon signed rank test) relative to baseline.
Figure 5
IL-10, TNF-α, and IFN-γ gene expressions in PBMCs, LNLC, and BALCs of 3 SIVagm-infected AGMs (SAB98007, SAB98008, and SAB98011) (A) and 2 mock-infected AGMs (SAB98001 and SAB98006) (B). Gray boxes indicate statistically significant increases (P < 0.05, Wilcoxon signed rank test) as compared with preinfection baseline values. See also legend to Figure 4.
Figure 6
Early pro- and antiinflammatory cytokine profiles in PBMCs and plasma. (A) _TNF-_α, IL-10, and _IFN-_γ gene expressions in PBMCs during primary SIVagm infection. Gene expressions were analyzed in 6 SIVagm-infected AGMs (SAB97008, SAB98013, SAB00020, SAB01013, SAB01015, and SAB02003) before and after infection, including very early time points (days 1 and 3 after infection). Values are expressed as _n_-fold increases relative to the calibrator. (B) Concentrations of IL-10 were measured in plasma collected from the same 6 SIVagm-infected AGMs and compared with 6 SIVmac251-infected rhesus macaques. Medium gray and dark gray boxes indicate statistically significant increases and decreases, respectively (P < 0.05, Wilcoxon signed rank test). The light gray box indicates a trend toward significant increase (IL-10 gene expression at day 10, P < 0.06, Wilcoxon signed rank test).
Figure 7
Assessment of CD25+ T cell percentages and of the expression levels of FoxP3 and TGF-β1. (A) CD4+CD25+ T cell percentages within lymphocytes of 6 SIVagm-infected AGMs (SAB97008, SAB98013, SAB00020, SAB01013, SAB01015, and SAB02003). (B) CD8+CD25+ T cell percentages within lymphocytes of these AGMs. (C) FoxP3 gene expression in PBMCs of these AGMs. (D) TGF-β1 gene expression in PBMCs of these AGMs. (E) Concentrations of TGF-β1 in plasma of these 6 AGMs. (F) Concentrations of TGF-β1 in plasma of 6 SIVmac251-infected rhesus macaques. See also legend to Figure 6 for medium gray and dark gray boxes.
Similar articles
- 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.
Karlsson I, Malleret B, Brochard P, Delache B, Calvo J, Le Grand R, Vaslin B. Karlsson I, et al. J Virol. 2007 Dec;81(24):13444-55. doi: 10.1128/JVI.01466-07. Epub 2007 Sep 26. J Virol. 2007. PMID: 17898053 Free PMC article. - Distinct expression profiles of TGF-beta1 signaling mediators in pathogenic SIVmac and non-pathogenic SIVagm infections.
Ploquin MJ, Desoutter JF, Santos PR, Pandrea I, Diop OM, Hosmalin A, Butor C, Barre-Sinoussi F, Müller-Trutwin MC. Ploquin MJ, et al. Retrovirology. 2006 Jun 26;3:37. doi: 10.1186/1742-4690-3-37. Retrovirology. 2006. PMID: 16800882 Free PMC article. - African non human primates infected by SIV - why don't they get sick? Lessons from studies on the early phase of non-pathogenic SIV infection.
Liovat AS, Jacquelin B, Ploquin MJ, Barré-Sinoussi F, Müller-Trutwin MC. Liovat AS, et al. Curr HIV Res. 2009 Jan;7(1):39-50. doi: 10.2174/157016209787048546. Curr HIV Res. 2009. PMID: 19149553 Review. - SIVagm infection of its natural African green monkey host.
Norley SG. Norley SG. Immunol Lett. 1996 Jun;51(1-2):53-8. doi: 10.1016/0165-2478(96)02555-2. Immunol Lett. 1996. PMID: 8811345 Review.
Cited by
- Walk on the wild side: SIV infection in African non-human primate hosts-from the field to the laboratory.
Jasinska AJ, Apetrei C, Pandrea I. Jasinska AJ, et al. Front Immunol. 2023 Jan 12;13:1060985. doi: 10.3389/fimmu.2022.1060985. eCollection 2022. Front Immunol. 2023. PMID: 36713371 Free PMC article. Review. - FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation.
Yero A, Shi T, Routy JP, Tremblay C, Durand M, Costiniuk CT, Jenabian MA. Yero A, et al. Front Immunol. 2022 Jul 29;13:962912. doi: 10.3389/fimmu.2022.962912. eCollection 2022. Front Immunol. 2022. PMID: 35967314 Free PMC article. - CCR5 as a Coreceptor for Human Immunodeficiency Virus and Simian Immunodeficiency Viruses: A Prototypic Love-Hate Affair.
Jasinska AJ, Pandrea I, Apetrei C. Jasinska AJ, et al. Front Immunol. 2022 Jan 27;13:835994. doi: 10.3389/fimmu.2022.835994. eCollection 2022. Front Immunol. 2022. PMID: 35154162 Free PMC article. Review. - So Pathogenic or So What?-A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research.
Kleinman AJ, Pandrea I, Apetrei C. Kleinman AJ, et al. Viruses. 2022 Jan 12;14(1):135. doi: 10.3390/v14010135. Viruses. 2022. PMID: 35062339 Free PMC article. Review. - The Hitchhiker Guide to CD4+ T-Cell Depletion in Lentiviral Infection. A Critical Review of the Dynamics of the CD4+ T Cells in SIV and HIV Infection.
Le Hingrat Q, Sereti I, Landay AL, Pandrea I, Apetrei C. Le Hingrat Q, et al. Front Immunol. 2021 Jul 21;12:695674. doi: 10.3389/fimmu.2021.695674. eCollection 2021. Front Immunol. 2021. PMID: 34367156 Free PMC article.
References
- Sousa AE, et al. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J. Immunol. 2002;169:3400–3406. - PubMed
- Hazenberg MD, et al. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS. 2003;17:1881–1888. - PubMed
- Deeks SG, et al. Immune activation set-point during early HIV infection predicts subsequent CD4+ Tt cell changes independent of viral load. Blood. 2004;104:942–947. - PubMed
- van Asten L, et al. Pre-seroconversion immune status predicts the rate of CD4 T cell decline following HIV infection. AIDS. 2004;18:1885–1893. - PubMed
- Apetrei C, Robertson DL, Marx PA. The history of SIVs and AIDS: epidemiology, phylogeny and biology of isolates from naturally SIV infected non-human primates (NHP) in Africa. Front. Biosci. 2004;9:225–254. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous