Changes in natural immunity during the course of HIV-1 infection

Abstract

SUMMARY The role of natural killer (NK) and lymphokine‐activated killer (LAK) cell‐mediated cytotoxiciry in AIDS has yet to be established. The objective of this study was to determine inducible LAK cell responses at different stages of HIV‐1 infection, and specifically to establish the participation of CD8 lymphocytes in these responses. Peripheral blood lymphocytes (PBL) were isolated from healthy seronegative (CDC‐0) subjects and HIV‐1 individuals who were clinically asymptomatic (Centre for Disease Control group 2, CDC‐2) or symptomatic (CDC‐4) with regard to secondary opportunistic infection (OI). LAK cells were generated upon incubation of PBL with IL‐2 and their cytolysis of K562 and U‐937 targets was determined using chromium release assays. The role of CD8+ lymphocytes as progenitors and effectors of these LAK cell responses was determined by immunomagnetic depletion of CD8+ cells from precursor PBL and LAK cells, respectively. LAK cell‐mediated cytotoxicities in HIV‐1‐infected individuals were reduced compared with scronegativc controls without any corresponding changes in the relative proportions of CD56+ (NK) cells among groups. Depletions of CD8+ subsets from either PBL or LAK cells dramatically reduced total LAK cytotoxic responses and LAK activities per unit CD56+ cell in the OI‐CDC‐2 scropositive population. No corresponding changes in LAK activities in seronegative control or HIV+/OI+ CDC‐4 groups were observed. Levels of LAK activity against K562 targets in CDC‐0/HIV and CDC‐4/HIV+ groups correlated with the percentage of CD56+ LAK cells; corresponding LAK activity in the CDC‐2/HIV+ group correlated with the percentage of both CD56+ and CD8+ subsets. These findings suggest that adaptive changes in non‐MHC restricted cytotoxic responses occur in HIV‐1 individuals at early stages post‐HIV infection, before the onset of opportunistic infection.

Risk factors that may modify the innate and adaptive immune responses in periodontal diseases

“…HIV infection has a profound effect on the cellular aspects of both innate and acquired immunity . In addition to a progressive decrease in CD4 + T‐cells (leading to impairment of adaptive immunity), HIV infection is also associated with defective CD8 + cytotoxic T‐lymphocytes and B‐cells . Furthermore, the innate immune system is also affected, including quantitative and qualitative changes in natural killer cells at all stages of HIV infection .…”

CD3 CD56 and CD3-CD56 Lymphocytes in the Cerebrospinal Fluid of Persons with HIV-1 Subtypes B and C

“…Although there are reports of increased NK cell activity during viremic HIV infection (Alter et al, 2004;Eller et al, 2009), during the chronic phase of HIV infection, NK cell numbers are low in the absence of ART (Azzoni et al, 2002;Alter et al, 2005;Mantegani et al, 2010), and most have a diminished ability to perform cytolysis and secrete cytokines (Cai et al, 1990;Brenner et al, 1993;Ullum et al, 1995Ullum et al, , 1999Azzoni et al, 2002;De Maria et al, 2003;Mavilio et al, 2003Mavilio et al, , 2006Fogli et al, 2004;Barker et al, 2007;Brunetta et al, 2009;Mantegani et al, 2010). With continued viral replication, the CD3 − CD56 dim subset previously expanded in acute infections decreased in number and function (De Maria and Moretta, 2008).…”

Heat shock protein-based therapeutic strategies against human immunodeficiency virus type 1 infection

“…However, it should be noted that basal and IL-2 inducible NK cellmediated cytotoxicity has been shown to decline progressively with advancing HIV disease. [63][64][65][66][67][68] Indeed, inducible NK cell function is among the most sensitive functional correlates of immunological dysfunction in HIV infection.…”