Peripheral S-phase T cells in HIV disease have a central memory phenotype and rarely have evidence of recent T cell receptor engagement.
Heightened proliferation and death of T lymphocytes may play a key role in human immunodeficiency virus (HIV) pathogenesis; however, the mechanism that mediates this effect and the phenotype of the proliferating T cells have not been clearly determined. We assessed S-phase cell frequencies and phenotype by ex vivo bromodeoxyuridine incorporation and flow-cytometric analysis in a group of 35 HIV-infected individuals. Frequencies of S-phase T cells were increased in HIV disease and were related to plasma HIV RNA levels but not to CD4 cell, total T cell, or total lymphocyte counts. S-phase cells were phenotypically defined as "central memory" cells (CD45RO+CD62L+CCR7+). Although activated (CD38+), S-phase cells lacked CD69 expression, rarely expressed CD25, and were not overrepresented among HIV-specific cells, as might have been expected if these cells had recently been activated by HIV antigens. Thus, in HIV infection, central memory T cells may be highly susceptible to bystander mechanisms of immune activation, leading to S-phase entry.
Sieg
Scott F
SF
Case Western Reserve University and University Hospitals of Cleveland, Center for AIDS Research, Cleveland, Ohio 44106-4984, USA. sfs2@case.edu
Rodriguez
Benigno
B
Asaad
Robert
R
Jiang
Wei
W
Bazdar
Douglas A
DA
Lederman
Michael M
MM
D000328:Adult; D015703:Antigens, CD / Q000502:physiology; D023241:Antiretroviral Therapy, Highly Active; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016196:S Phase / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell; D001973:Bromodeoxyuridine