Decreased PD-1 Expression on CD8 Lymphocyte Subsets and Increase in CD8 Tscm Cells in Children with HIV Receiving Raltegravir.
We investigated the effect of combination antiretroviral therapy (cART) on immune recovery, particularly on the percentages of PD-1-positive cells within the major leukocyte subsets. Cryopreserved peripheral blood mononuclear cells and plasma samples collected longitudinally from a subset of 13 children and adolescents (between 9.7 and 18.2 years old) who were enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1066 were used for this study. Immunophenotyping by flow cytometry was performed to determine the effect of raltegravir-containing cART regimen on the distribution of leukocyte populations, on the expression of PD-1 on T cell subpopulations, and on the expression of well-established markers of T cell activation (CD38 and HLA-DR) on CD8 T cells. C reactive protein (CRP), lipopolysaccharide (LPS), IL-6, and soluble CD163 were assayed in plasma samples by an enzyme-linked immunosorbent assay. Plasma viral loads were decreased in all subjects (by an average of 2.9 log units). The cART regimen, including raltegravir, induced changes in CD8 T cell subsets, consistent with an effective antiretroviral outcome and improved immunologic status, including increased percentages of CD8 stem cell memory T cells (Tscm). The percentages of CD8 PD-1-positive cells decreased significantly as compared with baseline levels. Among the proinflammatory markers measured in plasma, sCD163 showed a decline that was associated with cART. cART therapy, including raltegravir, over 48 weeks in children is associated with immune restoration, consistent with effective antiretroviral therapy, namely decreased percentages of PD-1+CD8+T cells, an increase in CD8 Tscm cells, and decreased levels of sCD163.
1 Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.|2 Flow Cytometry Core Laboratory, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.
Florin
F
Tuluc
1 Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.
Sergei
S
Spitsin
1 Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.
Nancy B
NB
Tustin
2 Flow Cytometry Core Laboratory, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.
Jennifer B
JB
Murray
1 Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.
Richard
R
Tustin
1 Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.
Laura A
LA
Schankel
3 Jacobi Medical Center , Albert Einstein College of Medicine, Bronx, New York.
Andrew
A
Wiznia
4 Department of Pediatrics, Stony Brook School of Medicine , Stony Brook, New York.
Sharon
S
Nachman
1 Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute , Philadelphia, Pennsylvania.|5 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
Steven D
SD
Douglas
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000293:Adolescent; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry*; D002648:Child; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D000074243:Immune Reconstitution; D016130:Immunophenotyping; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000737:chemistry*; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000068898:Raltegravir Potassium; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1
HIV; T cell immunity; antiretroviral therapy; clinical trials for antivirals; integrase inhibitors/drug discovery