Indicators of T-cell activation: correlation between quantitative CD38 expression and soluble CD8 levels in asymptomatic HIV+ individuals and healthy controls.
Increased activation of CD8+ T cells, particularly increased expression of CD38 antigen, has been shown to strongly correlate with progression of human immunodeficiency virus-positive (HIV+) individuals to acquired immunodeficiency syndrome (AIDS) and death. As part of a study evaluating responses to a recombinant gp160 vaccine, we have used quantitative three-color flow cytometry (QFCM) to further investigate the relationships among several measures of lymphocyte activation/immunological status. Parameters evaluated included 1) absolute circulating counts for the major lymphocyte phenotypes (T, B, NK) and selected activated/regulatory subsets believed to have clinical value in the monitoring of patients with HIV infection; 2) level of CD38 expression (antibody-binding capacity [ABC]) on the lymphocyte subsets defined by CD8, CD38, and HLA-DR; and 3) serum levels of soluble CD8. CD8+DR+CD38+ counts were found to be markedly increased (approximately 10-fold) in HIV+ individuals, whereas CD4+CD45RA+ counts were markedly decreased (approximately 5-fold). We confirmed previous reports that CD38 expression on CD8 T cells (here reported as CD38 ABC) are increased in asymptomatic HIV+ individuals as compared with healthy controls, and further found that CD38 ABC was elevated approximately 2-fold on CD8+DR+ cells as compared with CD8+DR- cells in healthy controls, and almost 2-fold further elevated on CD8+DR+ cells in HIV+ individuals compared with CD8+DR+ cells in healthy controls. In agreement with previous studies, we found increased serum CD8 levels (sCD8) and increased CD8+DR+ counts in asymptomatic HIV+ individuals. However, when sCD8 was expressed relative to CD8+DR+ cell counts (RsCD8), this index was found to be significantly decreased in HIV+ individuals. Although CD38 ABC on CD8+DR+ cells showed no correlation with sCD8, it was significantly correlated with RsCD8 in both HIV+ and HIV- individuals. Absolute lymphocyte counts were strongly correlated with both CD38 ABC and RsCD8 in HIV+ individuals. However, CD4 counts were correlated with CD38 ABC (but not RsCD8) in HIV+ patients and with RsCD8 (but not CD38 ABC) in HIV-controls. Our results suggest that QFCM is significant in understanding the role of CD8+DR+CD38+ cells in processes such as lymphocyte homeostasis and HIV-induced CD4-cell depletion.
Lenkei
R
R
CALAB Research, S:t. Görans Hospital, Stockholm, Sweden. rodica.lenkei@calab.se
Bratt
G
G
Holmberg
V
V
Muirhead
K
K
Sandström
E
E
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D016915:AIDS Vaccines; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis*; D018791:CD4 Lymphocyte Count; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009244:NAD+ Nucleosidase / Q000032:analysis / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D016915:AIDS Vaccines; D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1