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candidates for infection by HIV-1 in vivo are activated memory B cells and
centrocytes. These cells produce commutated Ig and are located in the vicinity
of T cells responsible for strong CD40 triggering and producing cytokines (IL-
2, IL-4, IL-10). However, CXCR4 is not fully functional on GC B cells and
stimulation of their BCR by FDC-trapped HIV-1 complexes would further
decrease CXCR4 expression. In the GC microenvironment, B-cell infection is
more likely to be due to these highly infectious opsonized virions presented by
FDC, possibly through the CD21/CD35 complex. We have not investigated the
requirement for chemokine receptors for C
0
-ADE HIV infection. Alternatively,
it is possible that mature B cells of any subset, once suitably activated, may
be infected by HIV-1. We have indeed shown that although phorbol ester-
activated B cells express less CD4 and complement receptors than resting B
cells, they are more susceptible to HIV-1 infection.
THE CD86/CD28 PAIR CONTROLS HIV-1 REPLICATION IN
INFECTED T CELLS
At each step of the T-dependent humoral response, a reciprocal dialogue takes
place between Ag-triggered B and T cells within the lymphoid tissue (Kelsoe,
1996). The small pool of infected CD4
T cells that produce HIV-1 RNA are
located in and around hyperplastic GCs of secondary follicles, in close contact
with Ag-presenting cells (APC), including DC in follicular and extrafollicular
areas and activated B cells within GC (Biberfeld et al., 1986; Fox et al., 1991;
Hufert et al., 1997). In blood and lymphoid tissue, interactions between DC
and CD4
T cells allow de novo infection of T cells and increase viral replica-
tion in T cells (Pinchuk et al., 1994; Pope et al., 1995; Weissman et al., 1996).
Activated B cells, particularly GC B cells, also provide costimulatory signals
that support HIV-1 replication and T cell activation in in vitro HIV-1-infected
T cells ( Krzysiek et al., 1998). At the optimal ratio (i.e., 10 B cells per T cell),
activated B cells were found to increase HIV-1 replication strongly, when p24
production was assessed or by using reverse transcriptase ( RT ) activity as a
marker. On day 8 postinfection, RT activity was 25 to 31 times higher with B
cells than without B cells. Similarly, more than 94% of CD4
T cells expressed
gp120 at their surface when cultured in the presence of B cells, whereas only
61% of CD4
T cells were gp120
in their absence ( Fig. 5.2).
In addition to T-cell receptor (TCR) stimulation, costimulation via CD28
triggering is required for a full T-cell response ( Boise, et al, 1995; Boussiotis et
al, 1996; June et al 1994). CD28, expressed on most CD4
and half of all CD8
T cells, interacts with two ligands present on most APC, the CD86 and CD80
molecules ( Boussiotis et al., 1996). Although CD80 and CD86 have the same
natural counterreceptors, CD28 and CTLA-4, they seem to control di¨erently
the TH2/TH1-type T-cell response ( Freeman et al., 1995; Kuchroo et al.,
1995), CTL generation, autoimmunity, and tumor growth (Boussiotis et al.,
1996). These two B7 molecules also exhibit di¨erent patterns of B-cell surface
