Down-regulation of interleukin-10 expression and production is associated with spontaneous proliferation by lymphocytes from human T lymphotropic virus type II-infected persons.
Cytokines from peripheral blood mononuclear cells (PBMC) from human T lymphotropic virus (HTLV)-II-infected persons were studied to delineate the mechanism(s) of spontaneous lymphocyte proliferation (SLP). Culturing HTLV-II-infected PBMC that spontaneously proliferate (SLP+) resulted in greater mRNA expression and production of interferon-gamma, interleukin (IL)-4, and IL-5, with a concomitant decrease in IL-10, than was seen with nonproliferating (SLP ) and normal PBMC. While IL-2 mRNA expression was higher, production was lower in SLP+ PBMC than in SLP and normal PBMC, implying that the proliferating cells are utilizing IL-2. Neutralization of IL-2 resulted in partial inhibition, suggesting that other cytokines also affect SLP. Addition of recombinant IL-10 inhibited the proliferation of SLP+ PBMC. Further, blocking costimulatory signals with monoclonal antibodies against CD80/CD86 resulted in increased IL-10 production with concomitant inhibition of SLP. The mechanism(s) underlying HTLV-II-associated SLP in vitro involve increased utilization of IL-2 and down-regulation of IL-10.
Dezzutti
C S
CS
Retrovirus Diseases Branch, Division of AIDS, STD, and Tuberculosis Laboratory Research, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. cyd5@cdc.gov
Sasso
D R
DR
Rudolph
D L
DL
Lal
R B
RB
D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000502:physiology; D051940:B7-2 Antigen; D002455:Cell Division; D002478:Cells, Cultured; D015536:Down-Regulation; D015491:HTLV-II Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D007963:Leukocytes, Mononuclear; D008214:Lymphocytes / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007376:Interleukin-2; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma