title: Differential effects of HIV viral load and CD4 count on proliferation of naive and memory CD4 and CD8 T lymphocytes.
abstract: We previously showed that HIV infection leads to expansion of a rapidly proliferating pool (s(1)) of CD4 and CD8 T lymphocytes. In the current study, we used in vivo labeling with bromodeoxyuridine to characterize the kinetics of naive, memory, and activated (HLA-DR(+)/CD38(+)) subpopulations of CD4 and CD8 T lymphocytes, and to examine the relationship between kinetic parameters and baseline CD4 counts, HIV viral load, potential markers of microbial translocation, and cytokine levels. Activated cells showed the highest proliferation rates, followed by effector and central memory cells, with naive cells showing the lowest rates, for both CD4 and CD8 T cells. HIV viral load correlated with s(1) of CD4 and CD8 effector memory cells, as well as CD8 naive cells, whereas CD4 cell counts correlated inversely with naive CD4 s(1). Endotoxin levels showed a weak negative association with CD4 but not CD8 s(1). INF-γ and TNF-α were associated with s(1) for CD4 and CD8 cells, respectively. Thus, HIV is the primary driving force behind the activation and proliferation of most subsets of both CD4 and CD8 T lymphocytes, whereas naive CD4 cell proliferation likely represents a homeostatic response. Microbial translocation does not appear to play an important role in this proliferation.
authors.affiliation: Biostatistics Research Branch, SAIC-Frederick Inc, NCI-Frederick, Frederick, MD, USA. srinivasulas@mail.nih.gov
authors.forename: Sharat
authors.initials: S
authors.lastname: Srinivasula
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Adelsberger
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Joshua
authors.initials: J
authors.lastname: Roark
authors.forename: Philip I
authors.initials: PI
authors.lastname: Lee
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.forename: Randy
authors.initials: R
authors.lastname: Stevens
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: H Clifford
authors.initials: HC
authors.lastname: Lane
authors.forename: Michele
authors.initials: M
authors.lastname: Di Mascio
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000502:physiology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D019562:Viral Load / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D001973:Bromodeoxyuridine