Decreased NK Cell FcRgamma in HIV-1 infected individuals receiving combination antiretroviral therapy: a cross sectional study.
BACKGROUND
FcRgamma is an immunoreceptor tyrosine-based activation motif (ITAM)-signalling protein essential for immunoreceptor signaling and monocyte, macrophage and NK cell function. Previous study from our laboratory showed that FcRgamma is down-regulated in HIV-infected macrophages in vitro. FcRgamma expression in immune cells present in HIV-infected individuals is unknown.


RESULTS
We compared FcRgamma expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcRgamma mRNA and protein levels were measured using quantitative real-time PCR and immunoblotting, respectively. CD56(+) CD94(+) lymphocytes isolated from blood of HIV-1 infected individuals had reduced FcRgamma protein expression compared to HIV-uninfected individuals (decrease = 76.8%, n = 18 and n = 12 respectively, p = 0.0036). In a second group of patients, highly purified NK cells had reduced FcRgamma protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021). Decreased FcRgamma expression in CD56+CD94+ lymphocytes was associated with reduced mRNA (51.7%, p = 0.021) but this was not observed for the smaller group of patients analysed for NK cell expression (p = 0.36).


CONCLUSIONS
These data suggest biochemical defects in ITAM-dependent signalling within NK cells in HIV-infected individuals which is present in the context of treatment with combination antiretroviral therapy.
Centre for Virology, The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
Edwin
E
Leeansyah
Jingling
J
Zhou
Geza
G
Paukovics
Sharon R
SR
Lewin
Suzanne M
SM
Crowe
Anthony
A
Jaworowski
D020816:Amino Acid Motifs; D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019002:CD56 Antigen / Q000096:biosynthesis; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000096:biosynthesis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction
D044966:Anti-Retroviral Agents; D019002:CD56 Antigen; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG