HOXB cluster genes in activated natural killer lymphocytes: expression from 3'-->5' cluster side and proliferative function.
The expression of HOXB cluster genes (i.e., B1 through B9) was evaluated in purified IL-2/IL-1 beta-activated NK lymphocytes from normal adult peripheral blood by RNase protection and reverse transcription-PCR. In quiescent NK cells these genes are essentially not expressed. After IL-2/IL-1 beta addition, we observed a coordinate induction wave in the 3'-5' HOXB cluster direction, i.e., from B1 through B9. As notable exceptions, B8 is silent, while B9 RNA is detected starting from 6 h through day 11. Furthermore, the 3' located B2/B3/B4 are expressed earlier and at higher level than the 5' located B5/B6/B7/B8. In IL-2/IL-1 beta-activated NK cells, treatment with antisense oligonucleotides targeting B2 mRNA causes a significant inhibition of both cell proliferation and expression of activation markers (i.e., IL-2R alpha-chain and transferrin receptor). These studies provide novel evidence of the role of HOX genes in adult NK cell proliferation. Thus, 1) a coordinate activation of HOXB genes from the 3'-->5' cluster side apparently underlies IL-2/IL-1 beta-induced NK cell activation. 2) Since NK cell activation and survival induced by IL-12 and c-kit ligand, respectively, are not associated with cell proliferation of HOXB gene expression, it is apparent that HOXB gene induction is specifically associated with IL-2-induced NK cell proliferation. 3) Studies with antisense oligomer targeting HOXB2 mRNA suggest an important role for 82 in NK cell proliferation, possibly in part via the IL-2R.
Quaranta
M T
MT
Department of Hematology-Oncology, Istituto Superiore, Sanità, Italy.
Petrini
M
M
Tritarelli
E
E
Samoggia
P
P
Carè
A
A
Bottero
L
L
Testa
U
U
Peschle
C
C
D000328:Adult; D000943:Antigens, Differentiation / Q000032:analysis; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D005801:Genes, Homeobox / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D005810:Multigene Family / Q000276:immunology* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000032:analysis; D013936:Thymidine / Q000378:metabolism
D000943:Antigens, Differentiation; D007375:Interleukin-1; D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D013936:Thymidine