Biology Reference
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selected issues, the hu-PBL-SCID mouse model o¨ers unique opportunities for
in vivo study of the e½cacy of novel immune interventions against HIV and,
more generally, against viral infections. In particular, even though the feasibil-
ity of a current use of hu-PBL-SCID mice in vaccine research is still a matter of
debate, we believe that hu-PBL-SCID mice can serve as very versatile and
practical animal models for investigating not only passive but also active im-
munity against HIV-1 infection. In general, studies on active immunization
have been hampered by di½culties in obtaining a primary human immune re-
sponse in the xenochimeric mice. The major limitations for developing a human
immune response in this model seem to be due to a limited human immune
repertoire, which is rapidly shaped by murine environment ( Tary-Lehmann et
al., 1994), the lack of appropriate human antigen-presenting cells (APCs) and,
®nally, to the onset of T-cell anergy ( Tary-Lehmann and Saxon, 1992). Despite
this, the generation of a primary human immune response in xenochimeric mice
has been reported in a few studies using di¨erent approaches to enhance an-
tigen presentation by using adjuvants, liposomes, and antigen-pulsed den-
dritic cells (Coccia et al., 1998; Walker et al., 1995, 1996), or by providing
a suitable microenvironment by engrafting SCID mice with human skin and
autologous PBLs ( Dehelm et al., 1998). Recently, we postulated that an e½-
cient immune response could be elicited in hu-PBL-SCID mice, provided that
appropriate antigen presentation could occur in vivo as a result of transfusion
of autologous APCs soon after reconstitution with hu-PBL, before the irre-
versible selection of xenoreactive human T-cell clones takes place. We recently
observed that infusion of autologous antigen-pulsed macrophages within a few
days of reconstitution, followed by a boost immunization after 7 days, gen-
erated a good antibody response (unpublished observations). Moreover, cul-
tured autologous dendritic cells, generated from monocytes after exposure to
granulocyte-macrophage colony-stimulating factors (GM-CSF ) and type I IFN
pulsed with inactivated HIV-1 induced the generation of a potent primary im-
mune response toward HIV-1 after injection in hu-PBL-SCID mice, as eval-
uated by the detection of speci®c human antibodies against the spectrum of
viral proteins. At 7 days after primary immunization, human antibodies proved
to be mostly IgM, whereas HIV-1-speci®c IgG1 antibodies were detected after
boosting (Santini et al., 2000). Notably, the antibodies detected in the sera of
mice injected with dendritic cells generated in the presence of IFN exhibited a
neutralizing activity in vitro against HIV-1 (our unpublished observations).
In conclusion, the SCID mouse models have considerably contributed to
generate the current knowledge on the pathogenesis and therapy of HIV-1 in-
fection over the last decade. These models, which are far more practical and less
expensive than other animal models for AIDS research, represent unique ap-
proaches for studying in vivo the interactions between HIV and human immune
cells. Even though a considerable amount of information on the pathogenesis of
HIV-1 infection has already been achieved by the use of hu-PBL-SCID mice,
we believe that the versatile characteristics of this practical animal model and
