Expansion and contraction of HIV-specific CD4 T cells with short bursts of viremia, but physical loss of the majority of these cells with sustained viral replication.

Abstract

Chronic infection with the HIV results in poor HIV-specific CD4 T cell proliferation, but more recent analyses using intracellular cytokine staining demonstrated that IFN-gamma-producing, HIV-specific CD4 T cells can be detected for years in HIV-infected subjects. Because it is not known whether the majority of HIV-specific T cells are lost or become dysfunctional, we examined the kinetics of the T cell response over an extended period of time using a panel of 10 HLA-DR tetramers loaded with HIV p24 peptides. Tetramer+ CD4 T cells were present at a relatively high frequency during acute infection, but the size of these populations substantially contracted following suppression of viral replication. Short-term cessation of antiretroviral therapy resulted in a burst of viral replication and concomitant expansion of tetramer+ CD4 T cells, and these populations again contracted following reinitiation of therapy. The kinetics with which these cell populations contracted were characteristic of effector T cells, a conclusion that was supported by their phenotypic (CCR7-CD45RA-) and functional properties (IFN-gamma+). Continued high-level viremia resulted in the physical loss of the majority of tetramer+ CD4 T cells, and the decline of HIV p24-specific CD4 T cells occurred more rapidly and was more substantial than the reduction of total CD4 T cell numbers. We conclude that the population of HIV p24-specific CD4 T cells is initially responsive to changes in the levels of viral Ags, but that the majority of these cells are lost in a setting of chronic viremia.

• Authors: Nilufer Seth, Daniel Kaufmann, Timothy Lahey, Eric S Rosenberg, Kai W Wucherpfennig
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 10 Pg. 6948-58 (Nov 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16272355 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HIV Core Protein p24
• HLA-DR Antigens
• Interferon-gamma

Topics

• Alleles
• Amino Acid Sequence
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Cell Proliferation
• HIV Core Protein p24 (metabolism)
• HIV Infections (immunology, pathology, virology)
• HIV-1 (immunology, physiology)
• HLA-DR Antigens (chemistry, genetics, metabolism)
• Humans
• In Vitro Techniques
• Interferon-gamma (biosynthesis)
• Kinetics
• Molecular Sequence Data
• Protein Structure, Quaternary
• Viremia (immunology, pathology)
• Virus Replication