Involvement of granzyme B and perforin gene expression in the lytic potential of human natural killer cells.
Natural killer (NK) cells (CD3- LGL) spontaneously kill K562 targets but are unable to kill Daudi cells in the absence of IL-2 stimulation. IL-4 is reported to prevent or inhibit the IL-2 driven lymphokine activated killer (LAK) generation in NK cells. Therefore, we asked whether the antagonistic effect of IL-4 on the IL-2 induced LAK activity might regulate the expression of genes encoding proteins involved in lysis, like perforin the pore-forming protein or associated to lysis like granzymes A and B. By using in situ hybridization we show that, besides inducing LAK activity, IL-2 stimulation increases the amount of perforin and granzyme B mRNA at the single cell level in 40 to 100% of the total CD3- LGL population, which suggests the preferential implication of a cell subset within the LGL population. In addition, our results indicate that the stimulatory effect of IL-2 can be down-regulated by IL-4 with respect to both LAK activity and granzyme B and perforin gene expression. Here again one can notice a decrease in the amount of specific mRNA per cell. These findings suggest that the modulation of the lytic machinery via lymphokines might be associated to the regulation of the lytic potentiality of NK/LAK cells.
Clement
M V
MV
INSERM Unit U93, Hôpital Saint-Louis, Paris, France.
Haddad
P
P
Soulie
A
A
Guillet
J
J
Sasportes
M
M
D002470:Cell Survival / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology*; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000235:genetics*
D007376:Interleukin-2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D015847:Interleukin-4; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases