Biology Reference
In-Depth Information
nisms underlying the phenotypic changes and decrease in NK cell frequency are
not clear, but our studies suggest strongly that these alterations are mediated
primarily by interaction of naive NK cells with target.
Reduced Ability of NK to Secrete Factors
We have previously proposed a model of NK cytotoxic function in which the
NK cells bind to the target and trigger the cytotoxic mechanism through the
secretion of cytotoxic factors ( Wright and Bonavida, 1982). Further, it is
now clear that cytotoxicity by NK cells can be mediated by degranulation of
granules containing perforin and granzymes, both of which contribute to target
cell lysis (Shi et al., 1992). In a previous study, we reported that, unlike NK
cells from normal individuals, NK cells from HIV-infected individuals were
functionally depressed and this depression was caused in part by failure of the
target cells to trigger the release of cytotoxic factors from the e¨ector NK cells
( Bonavida et al, 1986). However, the NK cells were not devoid of cytotoxic
factors inasmuch as activation by IL-2 stimulated the secretion of cytotoxic
factors but in quantities much less than in control NK cells. These studies thus
established one mechanism of functional inactivation of NK cells in which the
NK cells from HIV
individuals may lack appropriate receptors that signal cell
activation and degranulation.
Cytotoxic Functions
NK cells exert direct cytotoxicity against NK-sensitive target cells and anti-
body-dependent cellular cytotoxicity (ADCC) via the FcR against antibody-
control target cells.
NK Cytotoxicity. Several reports in the literature have demonstrated that NK
cytotoxic function is depressed in HIV-infected individuals and this function
deteriorates as a function of disease progression. Depressed NK functional
activity has been observed in asymptomatic and symptomatic HIV-infected
individuals and profound NK cell functional de®ciency has been reported in
acquired immunode®ciency syndrome (AIDS) ( Bonavida et al., 1986; Liu and
Janeway, 1990; Plaeger-Marshall et al., 1987; Voth et al., 1988). The reported
low NK cell numbers and their decreased functioning may contribute to the
susceptibility of HIV-infected subjects to HIV-related opportunistic infections,
Kaposi's sarcoma, and lymphomas.
Studies on the role of NK cytotoxicity in HIV-infected adult individuals
have yielded contradictory results (Blumberg et al., 1987; Fontana, 1986; Katz
et al., 1987, 1988; Ljunggren et al., 1989; Ojo-Amaize et al., 1989; Sirianni et
al., 1988; Tyler et al., 1990). The di¨erences may result from the use of di¨erent
strains of virus, targets cell lines, test conditions, and the addition or not of
exogenous antibodies for ADCC.
During a bout of moderate physical activity, HIV-seropositive individuals
