Markers of lymphocyte homing distinguish CD4 T cell subsets that turn over in response to HIV-1 infection in humans.
In HIV-1 infection, the abrupt rise in CD4 T cells after effective antiretroviral therapy has been viewed as a measure of HIV-1-related CD4 T cell turnover in the steady state. The early (2-4 wk) response is reportedly dominated by CD4 T cells with a memory (CD45RO) phenotype. It is controversial whether the measurement of steady-state kinetics identifies cells that otherwise would have been recruited into a short-lived, virus-producing pool or reflects lymphoid redistribution/sequestration. We performed detailed phenotypic and kinetic analysis of CD4 T cell subsets in 14 patients. Turnover occurs in memory (CD45RO) as well as naive (CD45RA) cells, if the latter are present at baseline. Most of the turnover occurs in those memory (CD45RO) and naive (CD45RA) cells that are programmed for recirculation through lymphoid organs (CD62L+ and CD44low), whereas very little turnover occurs in memory cells (CD45RO) destined for recirculation from blood to tissue (CD62L- and CD44high). Turnover occurs in both activated (CD25+ and HLA-DR+) and nonactivated populations, although it is restricted to CD38-positive cells, indicating that turnover does not measure cells that are already infected. More likely, turnover occurs in cells that replace infected cells or are on their way to becoming infected. Taken together, markers of lymphocyte trafficking better describe cell turnover related to virus replication than do naive and memory markers per se, and lymph organs, not tissue-destined cells or peripheral blood cells, appear to be the important site of virus replication and CD4 T cell turnover, destruction, and redistribution.
Hengel
R L
RL
HIV Immunology and Diagnostics Branch, Division of AIDS, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Jones
B M
BM
Kennedy
M S
MS
Hubbard
M R
MR
McDougal
J S
JS
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007156:Immunologic Memory; D007399:Interphase / Q000276:immunology; D007700:Kinetics; D019041:L-Selectin / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000097:blood; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D018448:Models, Immunological; D009244:NAD+ Nucleosidase / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000097:blood*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000821:virology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015415:Biomarkers; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D017493:Leukocyte Common Antigens; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1