Antigen burden is major determinant of human immunodeficiency virus-specific CD8+ T cell maturation state: potential implications for therapeutic immunization.
The majority of untreated human immunodeficiency virus (HIV) type 1-infected individuals ultimately develop uncontrolled viremia and progressive disease. Cytotoxic T lymphocytes (CTLs) are known to play an important role in controlling HIV-1 replication, which has led to an increasing interest in augmenting conventional antiretroviral therapy with therapeutic vaccination. The successful development of a therapeutic vaccine will rely on the ability to correlate an aspect of the immune response with clinical outcome. In this study, the CD8(+) T cell maturation status of antigen-specific cells in models of well and poorly controlled virus infections were compared, to show that a memory phenotype predominates when antigen loads are absent or low. In HIV-1 infection, the emergence of memory CD8(+) T cells was found to occur only in individuals with highly suppressed viral replication for an extended duration. Such assessments of the immune response may provide a refined measure of virus control.
Tussey
Lynda G
LG
Merck Research Laboratories, West Point, Pennsylvania 19486, USA. lynda_tussey@merck.com
Nair
Ushasree Sadasivan
US
Bachinsky
Margaret
M
Edwards
Bradley H
BH
Bakari
Janna
J
Grimm
Karen
K
Joyce
Joseph
J
Vessey
Rupert
R
Steigbigel
Roy
R
Robertson
Michael N
MN
Shiver
John W
JW
Goepfert
Paul A
PA
D019380:Anti-HIV Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006678:HIV / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008297:Male; D019562:Viral Load; D014780:Viruses / Q000276:immunology
D019380:Anti-HIV Agents; D015488:HIV Antigens