TY - JOUR
T1 - Immune activation, apoptosis, and treg activity are associated with persistently reduced CD4+ T-cell counts during antiretroviral therapy
AU - Piconi, Stefania
AU - Trabattoni, Daria
AU - Gori, Andrea
AU - Parisotto, Serena
AU - Magni, Carlo
AU - Meraviglia, Paola
AU - Bandera, Alessandra
AU - Capetti, Amedeo
AU - Rizzardini, Giuliano
AU - Clerici, Mario
PY - 2010/8/24
Y1 - 2010/8/24
N2 - Background: Persistently reduced CD4+ T-lymphocyte counts in the face of undetectable HIV viremia are seen in a sizable percentage of HIV-infected patients undergoing antiretroviral therapy (ART). We analyzed the immune correlates of this phenomenon. MATERIALS AND Methods: Sixty-seven HIV-infected patients with undetectable viremia (500 cells/μl or 16 years) was comparable. Peripheral blood mononuclear cell were stimulated with gag+env or with cytomegalovirus peptides. Activated T cells (Ki67), Treg lymphocytes (CD4/CD25high/Foxp3+), divided into naive and activated cells based on PD1 expression, interleukin (IL)-10 and transforming growth factor (TGF)-β production, annexin V, activation of caspases 8 and 9, Toll-like receptor (TLR)2 and TLR4 expression on immune cells, and plasma lipopolysaccharide (LPS) concentration were analyzed. Results: CD4/Ki67 T cells; plasma LPS; total, naive, and activated Treg; TLR2-expressing and TLR4-expressing Treg; IL-10 production; and early and late apoptotic CD4 T cells, were significantly increased in patients with undetectable viremia and CD4 cell counts less than 500 cells/μl after more than 7 years of ART. As previously shown, CD4 nadir were also lower in these individuals. Immune activation, LPS concentration, Treg, and degree of apoptosis were negatively correlated with CD4 cell counts. Conclusion: Lack of CD4 recovery in individuals in whom ART suppresses HIV replication is associated with complex immune alterations. Immune activation, likely driven by altered gut permeability and resulting in augmented Treg activity could play a pivotal role in this process.
AB - Background: Persistently reduced CD4+ T-lymphocyte counts in the face of undetectable HIV viremia are seen in a sizable percentage of HIV-infected patients undergoing antiretroviral therapy (ART). We analyzed the immune correlates of this phenomenon. MATERIALS AND Methods: Sixty-seven HIV-infected patients with undetectable viremia (500 cells/μl or 16 years) was comparable. Peripheral blood mononuclear cell were stimulated with gag+env or with cytomegalovirus peptides. Activated T cells (Ki67), Treg lymphocytes (CD4/CD25high/Foxp3+), divided into naive and activated cells based on PD1 expression, interleukin (IL)-10 and transforming growth factor (TGF)-β production, annexin V, activation of caspases 8 and 9, Toll-like receptor (TLR)2 and TLR4 expression on immune cells, and plasma lipopolysaccharide (LPS) concentration were analyzed. Results: CD4/Ki67 T cells; plasma LPS; total, naive, and activated Treg; TLR2-expressing and TLR4-expressing Treg; IL-10 production; and early and late apoptotic CD4 T cells, were significantly increased in patients with undetectable viremia and CD4 cell counts less than 500 cells/μl after more than 7 years of ART. As previously shown, CD4 nadir were also lower in these individuals. Immune activation, LPS concentration, Treg, and degree of apoptosis were negatively correlated with CD4 cell counts. Conclusion: Lack of CD4 recovery in individuals in whom ART suppresses HIV replication is associated with complex immune alterations. Immune activation, likely driven by altered gut permeability and resulting in augmented Treg activity could play a pivotal role in this process.
KW - antiretroviral therapy
KW - CD4\+ T lymphocytes
KW - cytokines
KW - HIV
KW - immune activation
KW - immunological nonresponders
KW - lipopolysaccharide
KW - PD-L1
KW - PD1
KW - toll-like receptor
KW - Treg cells
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UR - http://www.scopus.com/inward/citedby.url?scp=77955432632&partnerID=8YFLogxK
U2 - 10.1097/QAD.0b013e32833c93ce
DO - 10.1097/QAD.0b013e32833c93ce
M3 - Article
C2 - 20651586
AN - SCOPUS:77955432632
VL - 24
SP - 1991
EP - 2000
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 13
ER -