Biology Reference
In-Depth Information
apparently have an impaired ability to mobilize neutrophils, NK, and LAK
cells into the circulation. In some studies, training has also attenuated psycho-
logical stress. Given the impairment of resting immune function, the potential
immunosuppression from very intensive bouts of competitive exercise must be
avoided. Large-scale randomized and long-term studies of HIV are needed,
comparing the therapeutic value of exercise alone with that of psychotherapy or
a combined program of both (Shephard, 1998).
A study examined the role of stress hormones in the progression of HIV in-
fections. Cortisone and adrenoiorticotropic hormone (ACTH) inhibited NK cell
activity in vitro by NK from AIDS but not from normal donors. The selective
inhibitory e¨ects of cortisone and ACTH in patients with HIV infections are
consistent with the model that proposes that stress-related neurohormones and/
or neuropeptides may be involved in the progression of HIV infection (Nair et
al., 1995).
NK cell activity, either unstimulated or stimulated with INF-a, IL-2, and
LAK cell activity is suppressed in patients. The activity did not di¨er in patients
with or without AIDS. Asymptomatic patients have a higher activity than
symptomatic patients. The total CD16
cells was low in patients whereas the
percentage of CD16
,CD56
, and CD16
CD56
were either normal or ele-
vated ( Ullum et al., 1995).
ADCC. NK cells can mediate cytotoxicity against NK-resistant target cells by
ADCC through the trigger of the FcR (CD16) on NK cells by binding anti-
body-coated target cells. The same individual NK cell can mediate both cyto-
toxic functions (Bradley and Bonavida, 1982). The ADCC function of HIV-
derived NK cells was examined and was found to be normal, although the same
population was de®cient in NK cytotoxicity. These studies demonstrated that
the CD16 FcR on NK cells is functional and is independent of the NK trigger
receptor for direct cytotoxicity. Further, these studies corroborated the ®ndings
above that suggested that the lytic machinery is not completely abolished in
NK cells derived from HIV
individuals.
MECHANISMS OF NK FUNCTIONAL INACTIVATION AND DEPLETION
Anergy
NK cells undergo a state of functional anergy once they interact with the target
cells. During HIV infection, NK targets increase in frequency and, thereby,
through the interaction with NK cells, the NK cells become anergic in part and
in part undergo apoptosis.
Split Anergy in NK Cells from Normal Individuals. We and others have
reported that NK cells lose their cytotoxic function following their interaction
with target cells (Abrams and Brahmi, 1988; Jewett and Bonavida, 1995a). The
