Increased peripheral blood leukocyte subsets with regulatory phenotype in clinically stable long-term HIV-infected hemophilia patients on HAART may be beneficial and contribute to a decrease in autoimmunity.
After initiation of highly-active antiretroviral therapy (HAART), long-term HIV-infected hemophilia patients have been shown to lose autoantibodies against CD4(+) peripheral blood leukocytes (PBL), suggesting that HAART induces autoimmunity-blocking mechanisms. We compared cytokine levels and subpopulations of lymphocytes and dendritic cells (DC) in the blood of 40 long-term HIV(+) patients with those of 13 long-term HIV(-) hemophilia patients; 23 HIV(+) patients had a detectable retroviral load. Cell subsets were determined using flow cytometry and cytokine levels were measured using ELISA. HIV(+) patients showed higher proportions of DC subpopulations with immunostimulatory phenotypes (p < 0.01), CD8(+) PBL (p < 0.001), and IL-2 (p < 0.001) and sIL-2R plasma levels (p = 0.002) than HIV(-) patients. They also exhibited increased proportions of T PBL with immunosuppressive phenotypes such as CD3(+)CD4(+)CD25(+)Foxp3(+) (p = 0.001), and CD3(+)CD8(+)CD28(-)Foxp3(+) PBL (p < 0.001), and a decreased IL-7R expression on CD3(+)CD8(+) PBL (p = 0.001) compared to HIV(-) patients. Frequencies of CD3(+)CD4(+)CD25(+) PBL producing IL-2, IL-4, IL-10, IL-12, and/or IFN-gamma, and of CD3(+)CD4(+)CD28(-) PBL secreting IL-2 and/or IL-4 were lower in HIV(+) than in HIV(-) patients (p <or= 0.02). Proportions of CD4(+) PBL coated with IgG, IgM, and C3d were similar in HIV(+) and HIV(-) patients (p = n.s.). However, the proportion of CD4(+)gp120(+) PBL was higher in HIV(+) patients (p = 0.002), and associated with low CD3(+)CD4(+)CD25(+)Foxp3(+) PBL (p = 0.012). We conclude that long-term HIV-infected hemophilia patients on HAART show an adaptive immune response, presumably against HIV, in the presence of upregulated immunosuppressive T PBL, downregulated cytokine-producing CD4(+) PBL, and downregulated IL-7R expression on CD8(+) PBL. Increased immunoregulatory T PBL might decrease autoimmunity, thereby contributing to immunological reconstitution and stabilization of long-term HIV-infected hemophilia patients on HAART.
Daniel
Volker
V
Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. Volker.Daniel@med.uni-heidelberg.de
Naujokat
Cord
C
Sadeghi
Mahmoud
M
Zimmermann
Rainer
R
Huth-Kühne
Angela
A
Opelz
Gerhard
G
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D023241:Antiretroviral Therapy, Highly Active; D001323:Autoantibodies / Q000097:blood*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006467:Hemophilia A / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
D015703:Antigens, CD; D001323:Autoantibodies; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors