Interleukin-2 bolus therapy induces immediate and selective disappearance from peripheral blood of all lymphocyte subpopulations displaying natural killer activity: role of cell adhesion to endothelium.
As early as 10-15 min after the start of a 30 min interleukin-2 (IL-2) infusion, a rapid, virtually complete disappearance of all natural killer (NK) lymphocyte subpopulations (including both CD3- CD56+ and CD3+ CD56+ cells with either alpha/beta or gamma/delta T-cell receptor) was observed from peripheral blood. In contrast, the number of T lymphocytes (CD3+ CD56-) was unmodified for at least 2 h after IL-2 injection. The IL-2-induced, rapid disappearance from peripheral blood of NK and NK-like lymphocytes may be related to their massive adherence to the activated endothelium. In this regard, IL-2 infusion caused a very rapid rise of tumour necrosis factor-alpha (TNF-alpha) plasma concentration, whereas other cytokines, such as interferon-gamma (IFN-gamma), were induced only at later times. In vitro experiments indicated that IL-2, either alone or better combined with TNF-alpha, exerts a rapid and selective stimulatory effect on NK adhesion to endothelial cells. On the basis of these findings, we suggest that the activation of NK lymphocytes induced by IL-2, alone or combined with TNF-alpha, plays a key role in mediating the massive and selective adherence of NK and NK-like cells following IL-2 bolus infusion.
Salvo
G
G
Department of Hematology and Oncology, Istituto Superiore di Sanità, Rome, Italy.
Samoggia
P
P
Masciulli
R
R
Boccoli
G
G
Allavena
P
P
Mariani
G
G
Bullo
A
A
Montesoro
E
E
Bulgarini
D
D
Carlini
P
P
D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000628:therapy; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood* / Q000628:therapy; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000628:therapy; D008875:Middle Aged; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha