Dysregulation of interleukin-7 receptor may generate loss of cytotoxic T cell response in human immunodeficiency virus type 1 infection.
Virus-specific cytotoxic T lymphocytes (CTL) play a crucial role in modulating an immune response against human immunodeficiency type 1 (HIV-1) infection. The generation of effector cytotoxic cells from CTL precursors involves intricate interactions with antigen via T cell receptors (TcR) and soluble cytokines. Interleukin (IL)-7 can affect T cell maturation and differentiation. Here we report on a group of five HIV-1-positive individuals who tested negative for env- and gag-specific CTL activity. When exogenous recombinant human IL-7 was added as a stimulus to the cultures, none (0/5) of the CTL-negative individuals exhibited a CTL response. Individuals that were negative for HIV-1-specific CTL activity were found to lack IL-7 receptor (IL-7R) on CD8+ cells with a comparable reduction on CD4+ cells. Increased shedding of IL-7R in the culture supernatant was observed. A significant reduction in receptor number was detected by binding of 125I-labeled IL-7 and Scatchard analysis. The lack of IL-7R is probably not due to endogenous IL-7, since it was not detectable in the culture supernatants of the patients studied. HIV-1 proteins may cause down-modulation of IL-7R expression, either by producing an insufficient number of molecules or by rapid decay of IL-7R on T cells. These changes may alter the cells' capability to respond to the IL-7 growth signal, resulting in CTL failure and subsequent mishandling of the virus.
Carini
C
C
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
McLane
M F
MF
Mayer
K H
KH
Essex
M
M
D000328:Adult; D003602:Cytotoxicity, Immunologic; D004705:Endocytosis; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D015851:Interleukin-7 / Q000502:physiology; D008297:Male; D018123:Receptors, Interleukin / Q000502:physiology*; D020395:Receptors, Interleukin-7; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015686:Gene Products, env; D015683:Gene Products, gag; D015851:Interleukin-7; D018123:Receptors, Interleukin; D020395:Receptors, Interleukin-7