Biology Reference
In-Depth Information
an e¨ective HIV vaccine will require a strong CD8
T-cell response. Barouch
and co-workers recently demonstrated DNA vaccine-induced protective re-
sponses against a pathogenic SHIV-89.6 challenge in rhesus monkeys (Barouch
et al., 2000). Protection was associated with strong CTL responses ( IFN-g-
positive CD8
T cells) and preserved CD4
T-cell responses as determined by
cytokine ¯ow cytometry. Although the role of CTL seems to be crucial for
protective immunity induced by vaccines, and cytokine expression represents a
key component of the protective response, the exact function of these cells has
yet to be de®ned. The ability to simultaneously examine multiple parameters
makes cytokine (and chemokine) ¯ow cytometry an important tool to further
assess functional of responses of CD8
T cells to both therapeutic and pro-
phylactic HIV vaccine candidates. By combining this technique with class I
MHC TCR probes, for example, the functional heterogeneity (cytokine ex-
pression) of the antigen-speci®c CD8
T-cell response can be addressed (Appay
et al., 2000; He et al., 2001).
CONCLUSION
The immune system is the primary target of HIV. The clinical consequences are
the results of immune dysfunction and depletion. Within the past 5 years or so,
remarkable progress has been made in the understanding of the e¨ects of HIV
infection on the dynamics of speci®c T-cell immunity. Recently, new assays that
identify cytokine expression by single cells have been developed that enable the
functional identi®cation of antigen-speci®c T cells. The direct visualization of
T-cell e¨ector responses a¨orded by CFC allows an unparalleled ability to de-
termine the functional potential of phenotypically distinct T-cell subsets, ex-
pressing multiple cytokines and chemokines and thus the opportunity to eval-
uate the participation of these subsets in human immune responses in HIV
disease. A number of recent studies using these techniques have begun to ad-
dress the changes in antigen-speci®c responses and cytokine alterations caused
by antiretroviral therapies and vaccine-induced immune responses. The use of
antigen preparations consisting of peptide mixtures has allowed the simultane-
ous analysis of both CD4
and CD8
T-cell cytokine responses to multiple
epitopes independent of MHC haplotype and knowledge of T-cell repertoires.
Further investigations with these powerful techniques of cell-mediated immu-
nity in HIV disease and the analysis of T-cell responses to vaccines and anti-
retroviral drugs will be important for the development of new strategies for the
treatment of AIDS.
Acknowledgments. We thank the HIV
and CMV
subjects for their par-
ticipation in the analyses discussed in this study. Data for some of the results
illustrated in this review were provided by Barry M. Bredt, UCSF, San Fran-
cisco, CA.
