Biology Reference
In-Depth Information
T-CELL ACTIVATION ANTIGENS DURING HIV INFECTION
Immune activation was early recognized as being a characteristic feature of
HIV infection. Because HIV replicates in activated cells (Zack et al., 1988,
1990), the observation that an abnormal and augmented immune activation
takes place in this disease has an obvious, immediate clinical relevance. Addi-
tionally, immune-activated cells will be unable to respond to antigens, might
produce reduced amounts of soluble antiviral factors, and are more susceptible
to programmed cell death. A vast array of immune cells can phenotypically be
characterized as being activated in HIV-infected individuals, and activation is
seen in virtually each immune cell compartment. Thus, CD4
and CD8
T
lymphocytes as well as natural killer ( NK) cells show signs of immune activa-
tion. Markers of T-cell activation in HIV infection include, among others, in-
creased cell surface expression of CD45RO, CD25, CD28, CD38, HLA-DR,
and CD95 (Giorgi and Janossy, 1994).
CD45RO and CD45RA
In adult individuals with a normal immune system who are not infected with
HIV, the majority of T cells are memory cells that have been exposed to
antigen, although up to 45% of CD4 cells may be naive (Autran et al., 1997).
Naive T cells express the CD45RA as well as other markers including CD62L
( L-selectin) and CD44 marker ( Farber, 2000; Sprent, 1994). This results in
di¨erent homing patterns, with naive cells preferentially migrating to lymph
nodes and memory cells more prone to migrate into peripheral tissues, partic-
ularly when an in¯ammatory process is present ( Farber, 2000; Sprent, 1994).
Although published estimates vary, a current estimate for the turnover rate of
naive T cells in non-HIV-infected individuals is several (3.5±6) years. Because
the death rate of naive cells is suggested to be very low, this turnover is proba-
bly mainly associated with cell division and maturation ( Finzi and Siliciano,
1998; Hellerstein and McCune, 1997). Resting, naive CD4 T cells are not very
susceptible to HIV infection ( Finzi and Siliciano, 1998; Hellerstein and
McCune, 1997), whereas the activated naive T cell (CD45RA
), which has a
lifetime of several weeks after antigen stimulation, is extremely susceptible to
HIV infection (Finzi and Siliciano, 1998; Hellerstein and McCune, 1997). After
most of these cells have died, a few long-lived memory CD4 cells that are ready
to be activated by speci®c peptide±major histocompatibility complexes persist
in a resting state, with a turnover time (0.4±1.1 years) that is shorter than the
characteristic of naive T cells (Cossarizza, 1997). Resting and activated memory
(CD45RO
) T cells are therefore the primary targets of HIV infection (Cos-
sarizza, 1997), but, despite these cells being preferential or selective targets for
HIV, the proportion of naive/memory CD4 cell ratio decreases over the course
of HIV infection for reasons that are as yet unknown. Very recently, it has been
shown that the memory/naive ratio is altered even in uninfected newborns of
