Biology Reference
In-Depth Information
HIV-infected mothers, suggesting that CMI and T-cell maturation may be
altered even in HIV-uninfected newborns of HIV-infected mothers (Clerici
et al., 2000).
The presence of both naive and memory T cells is associated with the con-
dition of health. Thus, although naive T cells are important for their ability to
respond to newly encountered pathogens, the presence of memory T cells is
critically important in allowing the development of secondary immune re-
sponses. Recent data show that the number of memory CD4
T cells is in-
creased much more promptly than that of naive T lymphocytes in HIV-infected
individuals undergoing HAART (Autran et al., 1997; Gray et al., 1998; Wend-
land et al., 1999). Thus, whereas increases in CD4
45RO T cells are observed
within a few months after the initiation of combination therapy, changes in the
number of naive T lymphocytes are not detected for years in HIV patients under-
going HAART. This situation is characteristic of adult patients treated with
HAART, as the number of naive T cells is promptly restored in HAART-
treated pediatric patients (Vigano et al., 1999a). The ability of pediatric pa-
tients to repopulate peripheral blood with naive CD4
T cells upon the initia-
tion of therapy was recently shown to be correlated with changes in the volume
of thymus ( Vigano et al., 2000) (Table 3.2).
CD25
CD25 is the a subunit of the IL-2 receptor. CD25 is expressed on activated
T lymphocytes, where it forms a trimeric complex with the b and g subunits of
the IL-2 receptor. The trimeric form of this receptor binds to IL-2 in a much
tighter way, thus increasing the a½nity of the signaling receptor for IL-2. The
percentage of CD4
T cells expressing CD25 is augmented in HIV infec-
tion; this increase is suggested to be directly correlated with increasing disease
severity (Mahalingham et al., 1993, 1995). Interestingly, CD4
/CD25
T lym-
phocytes are augmented even in HIV-infected individuals undergoing HAART.
HAART-induced modulation of CD25-expressing CD4
T cells might be as-
sociated with the observation that, whereas suppression of HIV viremia can be
achieved in the majority of HIV-infected individuals by antiretroviral therapy,
the e½cacy of these therapies in reconstituting immune function is less than
dramatic. Thus, recent studies have suggested that CD25-expressing CD4
T
cells are anergic suppressor cells (Thornton and Shevac, 1998, 2000) that can
anergize CD8
T lymphocytes (Shimizu et al., 1999) and impair CMI via the
production of IL-10 ( Papiernick et al., 1998). An additional mechanism by
which CD4
CD25
T cells can dampen T-cell activation was recently postu-
lated by Cederbom and colleagues, who showed these lymphocytes to be able to
down-regulate the expression of CD80 and CD86 on the surface of antigen-
presenting cells (Cederbom et al., 2000). Finally, the expression of CD25 was
suggested to di¨erentiate CD4
T cells that are latently (CD25
ÿ
) or produc-
tively (CD25
) infected (Borvak et al., 1995).
