Effect of interleukin-2 on generation of natural killer cells: role of major histocompatibility complex class I in B6 and TAP-1-/- mice.
Long-term bone marrow cultures were used to investigate the effect of IL-2, a cytokine widely used in immunotherapy, on natural killer cell differentiation. Specifically, the role of MHC was evaluated by comparing normal B6 and class I-deficient TAP-1-/- mice. The number of cells generated after a 13-day culture was the same in cell cultures from TAP-1-/- or B6 mice but the relative number of natural killer cells, identified as NK-1.1+CD3- cells by flow cytometry analysis, was increased in TAP-1-/- compared to B6 cultures (74.4% and 63.9%, respectively). Addition of an anti-class I mAb determined a strong inhibition of natural killer cell generation in B6 cultures, and its effect was specific since no effect was seen in TAP-1-/- cell cultures. TAP-1-/- natural killer cells or the few natural killer cells escaping the inhibitory effect of anti-class I mAb, were less cytotoxic than total B6 natural killer cells against target cell lines of different haplotype.
Delfino
D V
DV
Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, Italy. farmaco@unipg.it
Di Marco
B
B
Marchetti
C
C
Bartoli
A
A
Ayroldi
E
E
Bruscoli
S
S
Agostini
M
M
Spinicelli
S
S
Zollo
O
O
Migliorati
G
G
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D001613:beta 2-Microglobulin / Q000235:genetics
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D007376:Interleukin-2; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin