Expression of regeneration and tolerance factor correlates directly with human immunodeficiency virus infection and inversely with hepatitis C virus infection.
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause two of the most prevalent debilitating viral infections. HIV appears to induce a skewing toward a Th2 response, while in HCV infection a Th1 response appears to dominate. Regeneration and tolerance factor (RTF) may participate in driving or sustaining a Th2 cytokine response. The expression of RTF on CD3(+) T cells of HIV-seropositive (HIV(+)) individuals is increased. The purpose of this study was to compare the expression of RTF during HIV infections with that during HCV infections. Three-color flow-cytometric analysis of peripheral blood collected from HIV(+) HCV-seropositive (HCV(+)), HIV- and HCV-seropositive (HIV(+) HCV(+)), and HIV- and HCV-seronegative (HIV(-) HCV(-)) individuals was performed. Levels of RTF expression on T-lymphocyte subsets from these groups were compared, as were levels of RTF expression on activated T cells expressing CD38 and HLA-DR, to determine the relationship of RTF expression to these infections. We demonstrated that the expression of RTF on surfaces of T cells from HIV(+) individuals is upregulated and that its expression on T cells from HCV(+) individuals is downregulated. A twofold increase in the mean channel fluorescence of RTF on CD3(+) T cells was seen in both HIV(+) and HIV(+) HCV(+) individuals compared to HIV(-) HCV(-) individuals. HCV(+) individuals had lower levels of RTF expression than HIV(-) HCV(-) individuals (P < 0.005 for CD4(+); P < 0.0005 for CD8(+)). In terms of percentages of T cells expressing RTF, the groups were ranked as follows: HIV(+) > HIV(+) HCV(+) > HIV(-) HCV(-) > HCV(+). The results indicate that RTF expression correlates with HIV-associated immune activation and may be associated with Th2-type responses.
Sung
C C
CC
Clinical Immunology Laboratory, Department of Microbiology and Immunology, North Chicago, Illinois 60064, USA.
Boomer
J S
JS
Givens
T S
TS
DuChateau
B K
BK
Lepe
M R
MR
Feller
A
A
Westerman
M P
MP
Gilman-Sachs
A
A
Chedid
A
A
Beaman
K D
KD
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009244:NAD+ Nucleosidase / Q000276:immunology; D011257:Pregnancy Proteins / Q000096:biosynthesis* / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D006180:Proton-Translocating ATPases
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017252:CD3 Complex; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase; D011257:Pregnancy Proteins; D013491:Suppressor Factors, Immunologic; C498154:CD38 protein, human; C498155:Cd38 protein, mouse; C525845:ATP6V0A2 protein, human; D006180:Proton-Translocating ATPases