Clinical Progression of HIV Infection: Role of NK Cells

Abstract

Bruunsgaard H, Pedersen C, Skinhøj P, Pedersen BK. Clinical Progression of HIV Infection: Role of NK Cells. Scand J Immunol 1997;46:91-95 The purpose of the study was to examine how immune parameters related to non-major histocompatibility complex (MHC) restricted cytotoxicity changed with respect to progression and duration of human immunodeficiency virus (HIV) infection. Forty-one HIV seropositive subjects with a known time for seroconversion were included. The major finding was that a low percentage and number of natural killer (NK) cells were found in the group who had a rapid progression to acquired immune deficiency syndrome (AIDS) (less than 70 months following seroconversion) compared with those progressing more slowly to AIDS (more than 70 months following seroconversion). Furthermore, a significant correlation was found between the number of months from seroconversion to the diagnosis of AIDS and percentages of CD16þ cells (r s ¼ 0.811, P < 0.01), CD56þ cells (r s ¼ 0.647, P < 0.05), and CD16þCD56þ cells (r s ¼ 0.839, P < 0.01) as well as the concentration of CD16þCD56þ cells in the blood (r s ¼ 0.699, P < 0.05). No differences were found in percentages and concentrations of NK cell subsets between subjects with a long history (more than 6 years) versus a short history (less than 6 years) of HIV infection without AIDS. Furthermore, no negative correlations were found between the concentration of any NK subsets and the number of months since seroconversion in HIV seropositive individuals without AIDS. The total concentration of CD16þ, CD56þ, and CD16þ CD56þ cells was lower in the group of HIV seropositive subjects compared with HIV seronegative subjects (age and sex matched), and the concentration of CD16þ cells was lower in those with AIDS than in those without AIDS. In conclusion, low concentration of NK cells in the blood was associated with a more rapid disease progression, indicating that defective non-MHC restricted cytotoxicity may be associated with HIV disease progression.

Characterization of CD56–/CD16+natural killer (NK) cells: A highly dysfunctional NK subset expanded in HIV-infected viremic individuals

“…When the HIV viral load is high, there is a dramatic expansion of CD56 Ϫ ͞ CD16 ϩ (CD56 Ϫ ) NK cells, a subset that is represented at a very low frequency in healthy HIV-negative and aviremic HIV-infected individuals (10,13,18). Of note, HIV-1 viremia does not seem to affect the CD56 bright NK cells; however, it is associated with a statistically significant decrease of the CD56 dim ͞CD16 ϩ NK subpopulation (13,20), and it has also been related to a rapid and early progression to AIDS (26). The presence of an expanded CD56 Ϫ NK cell population among HIV viremic individuals has been associated with significantly reduced spontaneous NK cytolytic activity as compared with that of aviremic individuals or healthy donors (13).…”

HLA-Bw4-B*57 and Cw*18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil

“…HLA-Bw4 is one of the inhibitory or activating ligands for KIR 18,19 that control the natural killer (NK) cell cytotoxic activity. As a component of the innate immune system NK cells might have a very important role in the defense of the HIV-1 infected host, 20 possibly controlling the viremia through lysis of HIV-infected cells. 21,22 Genetic association studies and functional assays report the importance of HLABw4 in the pathogenesis of AIDS.…”

Natural Killer Cell Function Is Well Preserved in Asymptomatic Human Immunodeficiency Virus Type 2 (HIV-2) Infection but Similar to That of HIV-1 Infection When CD4 T-Cell Counts Fall

“…In addition, they can produce higher levels of cytokines and chemokines (4) that may enhance the adaptive immune response to pathogenic infection and therefore play an important role in controlling infections. A few studies in HIV-1 infection have suggested that NK cell activity may indeed be important in protective immunity: Rapid progression to AIDS has been associated with reduced NK cell activity and a decrease in NK cell numbers (6,32). NK cells from HIV-1-infected subjects were also found to secrete CC chemokines with the ability to suppress autologous HIV replication in vitro (10,17,25) and high gamma interferon (IFN-␥) release was found to be associated with NK cell number in interleukin (IL)-2 therapy during AIDS (16).…”