Despite significant technical advances that have permitted an increasingly more quantitative and detailed study of virus-specific cellular immunity over the past few years, our understanding of the nature of immunological control in rare cases of non-progressive HIV infection and diminished control in the majority of untreated chronically infected patients remains incomplete. This review will summarize recent findings and points of controversy within areas of active investigation of the cellular immune response to HIV.
It is now appreciated that high frequencies of virus-specific CD8 T cells are readily detectable in chronic HIV infection, but do not restrict viral replication. For this reason, attention has shifted to qualitative features of the host immune response that might accurately determine the restriction of viral replication. A number of qualitative changes in the phenotype, cytokine secretion, and proliferative capacity of HIV-specific CD8 T cells of progressors have recently been described.
Given that the desired response to the majority of vaccines in pre-clinical or clinical testing is to stimulate cellular immunity in an attempt to alter disease progression, understanding these qualitative features is of particular relevance. Further study will probably yield critical information for the means to stimulate effective immunity in vaccinees, prevent the loss of control of viral replication upon infection of vaccinees, or induce durable immunological control in humans already infected with HIV.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Correspondence to Mark Connors, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11B-09, 10 Center Dr MSC 1876, Bethesda, MD 20892-1876, USA Tel' +1 301 496 8057; fax: +1 301 402 0070; e-mail: firstname.lastname@example.org