Most of the studies investigating antiviral immunity have predominantly focused on CD8 T cells. However, numerous recent studies have highlighted the importance of HIV-1-specific CD4 T cells in the antiviral immune response, and have also revealed the high level of complexity and heterogeneity of the virus-specific CD4 T-cell responses. An understanding of the role of these key players in the antiviral immune response is of fundamental importance.
A comprehensive investigation of several features of virus-specific CD4 T-cell responses, including the magnitude, breadth, function and phenotype, has recently been performed. In particular, HIV-1-specific CD4 T-cell responses have been studied in different stages of HIV-1 infection, i.e. acute and chronic phase, under conditions of spontaneous (long-term non-progressors) or antiviral therapy-mediated control of virus replication or uncontrolled virus replication. Different phenotypical and functional patterns of HIV-1-specific CD4 T-cell responses were associated with different conditions of controlled versus uncontrolled virus replication, thus allowing the identification of signatures of protective immune responses. Robust and diverse virus-specific CD4 T-cell responses have been observed. These responses, however, were not predictive of nonprogressive versus progressive HIV-1-associated disease.
There is an urgent need to delineate the immune correlates of protective T-cell responses in order to develop novel immunological markers to evaluate the degree of immune restoration of antiviral therapy as well as the potential effectiveness of HIV vaccine-induced T-cell immune responses.
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
Correspondence to Alexandre Harari, PhD, Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue Bugnon, 1011 Lausanne, Switzerland Tel: +41 21 3141071; fax: +41 21 3141070; e-mail: email@example.com
Sponsorship: This work was supported by research grants from the Swiss National Foundation (FN 3100-058913/2) and the European Commission (QLK2-CT-1999-01321).