Interferon-gamma receptors in HIV-1 infection.
We studied in vitro production of interferon-gamma and expression of interferon-gamma receptors (R1 and R2) by the peripheral blood mononuclear cells of 24 HIV-1-infected patients and 12 healthy volunteers. Interferon-gamma production was lower in HIV-1-infected patients compared with healthy volunteers (p < 0.05), and it further declined in patients with lower CD4+ T-cell counts. In contrast, expression of interferon-gamma R1 by CD4+ T lymphocytes was higher in HIV-infected patients than healthy volunteers (25% versus 10%, p < 0.05). In the HIV-infected group, interferon-gamma R1 expression increased with a decline in CD4+ T-cell count (r = -0.64, p < 0.001). Interferon-gamma R2 expression directly correlated with interferon-gamma R1 expression (p < 0.001). When stimulated with heat-killed Mycobacterium avium complex (MAC) and phorbol myristic acetate (PMA), the mononuclear cells of patients with advanced HIV-1 infection had lowered ability to produce additional interferon-gamma (either MAC or PMA) and interferon-gamma receptors (MAC). In conclusion, with progression of HIV-1 infection, interferon-gamma production declines whereas expression of interferon-gamma receptors (R1 and R2) increases. Persistent upregulation of both interferon-gamma R1 and R2 receptors probably favors development of type 2 T-helper cells environment and promotes viral replication. This dysfunction in the interferon-gamma pathway contributes to a further impairment in cellular immune function in patients with advanced HIV-1 infection, which may further increase susceptibility to opportunistic infections.
Koirala
Janak
J
Division of Infectious Diseases, Southern Illinois University, School of Medicine, Springfield, Illinois 62794-9636, USA. jkoirala@siumed.edu
Adamski
Alys
A
Koch
Lori
L
Stueber
Danielle
D
El-Azizi
Mohammed
M
Khardori
Nancy M
NM
Ghassemi
Mahmood
M
Novak
Richard M
RM
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017471:Receptors, Interferon / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor