Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy.
To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.
Kovacs
J A
JA
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, USA. jkovacs@nih.gov
Vogel
S
S
Metcalf
J A
JA
Baseler
M
M
Stevens
R
R
Adelsberger
J
J
Lempicki
R
R
Hengel
R L
RL
Sereti
I
I
Lambert
L
L
Dewar
R L
RL
Davey
R T
RT
Walker
R E
RE
Falloon
J
J
Polis
M A
MA
Masur
H
H
Lane
H C
HC
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013618:Tachyphylaxis; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1