Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS.
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.
Kornfeld
Christopher
C
Unité de Biologie des Rétrovirus, Institut Pasteur, Paris, France.
Ploquin
Mickaël J-Y
MJ
Pandrea
Ivona
I
Faye
Abdourahmane
A
Onanga
Richard
R
Apetrei
Cristian
C
Poaty-Mavoungou
Virginie
V
Rouquet
Pierre
P
Estaquier
Jérôme
J
Mortara
Lorenzo
L
Desoutter
Jean-François
JF
Butor
Cécile
C
Le Grand
Roger
R
Roques
Pierre
P
Simon
François
F
Barré-Sinoussi
Françoise
F
Diop
Ousmane M
OM
Müller-Trutwin
Michaela C
MC
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018946:Chemokine CCL5 / Q000378:metabolism; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D016753:Interleukin-10 / Q000097:blood; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D054389:Receptors, CCR1; D019713:Receptors, CCR5 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014766:Viremia
C515300:CCR1 protein, human; D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D012367:RNA, Viral; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D007371:Interferon-gamma