Immune Dysregulation and T-Cell Activation Antigens in HIV Infection - Cellular Aspects of HIV Infection - page 40

undergo rapid CD95-mediated apoptosis upon antigen stimulation. TH2 clones
are also known preferentially survive in vitro cell cultures. These ®ndings are
justi®ed by the observation that, whereas both types of clones express CD95,
only TH2 clones express high levels of a CD95-associated phosphate that in-
hibits CD95 signaling. Interestingly, a potent expression of CD95 as well as
susceptibility to CD95 ligation seem to be predominant in primed/memory
(CD45RO) T cells, suggesting that virus-driven T-cell activation is responsible
for the increased apoptosis (Bohler et al., 1997b). This is also supported by
®ndings of a prompt down-regulation of increased CD95L expression in T cells
of patients undergoing antiretroviral therapy ( Bohler et al., 1997c). This de-
crease is associated with reductions in HIV plasma viral load.
In addition to mechanisms of accelerated suicide or paracrine death, CD95-
induced apoptosis during HIV infection may be mediated by cytotoxic e¨ector
cells. The magnitude of the CTL response during HIV infection and the high
proportion of CD95 compliant target cells among patients' lymphocytes argue
for a deleterious role of CTL against activated T cells. In the contest of HIV
pathogenesis, the persistence of continuously activated antiviral CTL would
thus be associated with CD95L expression and, therefore, with the ability to kill
both virus-infected cells and noninfected, activated compliant CD95 target
cells. The exacerbation of the CD95 system would drive antiviral CTL in a
deleterious role and particulary in the physiological elimination of CD4 T cells,
irrespective of the infected status. This would contribute to the collapse of the
immune system.

PHENOTYPIC MARKERS PREFERENTIALLY EXPRESSED ON TH1
AND TH2 LYMPHOCYTES

Whereas TH1 and TH2 lymphocytes are still de®ned on a functional basis (i.e.,
the predominant cytokine production pro®le), a series of phenotypic markers
may be preferentially expressed by either of the T-helper types. These markers
include CD7, CD30, and some chemokine receptors (CXCR3, CCR3, CCR4,
and CCR8) (see Table 3.4).

CD7
CD4 T-helper lymphocytes can be di¨erentiated in two subpopulations based
on the expression of the CD7 marker. CD4 CD7 T lymphocytes preferen-

T A B L E 3.4. Phenotypic Markers Preferentially Expressed by TH1 or TH2
Lymphocytes

TH1 lymphocytes CD7* SLAM CCR3 CCR4 CCR8

TH2 lymphocytes CD30 CXCR3

* On CD4 CD57 T cells.