B Cells in the Line of Sight of HIV-1 - Cellular Aspects of HIV Infection - page 79

HIV-1 reservoir and viral replication site colocalizes with the area of highest
CD86 expression, within the light zones of GC. Thus, CD86-mediated inter-
actions, which take place during the response to each T-dependent antigen, also
stimulate HIV-1 replication in T cells.
IN SITU EXPRESSION OF CD80 AND CD86 WITHIN GC OF HIV B
PATIENTS
As CD80- and CD86-mediated interactions di¨erentially regulate HIV-1 repli-
cation in in vitro infected T cells, we compared the in situ expression of CD80
and CD86 in HIV and HIV ÿ lymphoid organs. We observed enlarged, irreg-
ularly shaped GCs surrounded by a limited, frequently disrupted, IgD mantle
zone in hyperplastic HIV lymph nodes (LNs), as previously shown ( Baroni
and Uccini, 1990; Racz et al., 1986) (Fig. 5.3F ). CD4 T cells were scattered in
the GC of HIV patients rather than being limited to the light zone as in nor-
mal tonsils and HIV ÿ LNs. There were signi®cantly more CD57 cells in the
extrafollicular zone and in CD8 T cells in the GC of hyperplastic HIV LNs,
consistent with previous data (Borthwick et al., 1994; Koopman et al., 1997)
suggesting that these in®ltrated CD8 T cells are involved in FDC network
disruption and the destruction of HIV-infected cells (Koopman et al, 1997).
CD8 cells also produce chemokines that suppress HIV infection (Cocchi et al.,
1995) and regulate T-cell homing, so chemokines/chemokine receptors may
also impair B-cell homing ( Forster et al., 1997) or function ( Kimata et al.,
1996). The increase in CD38 expression in the extrafollicular zone in HIV
patients is consistent with the strong and persistent activation of T cells dur-
ing HIV infection ( Kestens et al., 1994). We also found high levels of CD95
expression in the extrafollicular zone of HIV LNs. This probably increases
T-cell sensitivity to apoptosis, as reported for peripheral blood T cells (Silvestris
et al., 1996).
The FDC network, uniformly distributed in normal and hyperplastic HIV ÿ
GC, was frequently disrupted in HIV GC. Similar results were obtained by
Baroni et al. ( Baroni and Uccini, 1990). There was no signi®cant change in the
pattern of expression of most B-cell markers, but polarization of the HIV GC
was lost, as shown by Ki67, CD10, and CD77 staining, showing a random
distribution of centroblasts throughout the GC (Fig. 5.3E ). There is no obvious
marker for centrocytes but they do not express Ki67 and CD77, are CD38 and
CD95 , and have high levels of CD86. Based on this pattern, we observed that
centrocytes, present only in the light zone of normal and hyperplastic HIV ÿ
GC, were distributed throughout the GC of HIV patients (Fig. 5.3F ). It is
therefore unlikely that a particular population of GC B cells increases during
HIV-induced hyperplasia.
CD86 cells limited to the light zone of normal tonsils and HIV ÿ hyper-
plastic LNs were dispersed throughout the GC in HIV patients (Fig. 5.4F )
but the intensity of CD86 staining was similar for all sections studied. Unlike