Functional and phenotypic modifications induced by IL-4, as single agent or in combination with IL-2, on PBMC preactivated in vivo by alpha-interferon + interleukin-2 therapy.
The effect of human IL-4, used as a single agent or in combination with low or high dose IL-2, upon LAK-cell proliferation and activation has been tested on PBMC from patients treated with alpha 2-IFN and IL-2. Four days in vitro culture with IL-4 did not induce any LAK-cell activation; IL-4 induced the proliferation of CD3+ CD4+ T-cells, but decreased the percentage of NK cells in culture samples. When combined with high dose IL-2, IL-4 improved the recovery of MN cell without modification of T-cell subsets; however, IL-4 had no major effect on IL-2-induced NK or LAK cell activity. The combination of IL-4 and low dose IL-2 still significantly improved the total MN cell recovery but did not modify the distribution of T and NK lymphocytes; IL-4 inhibited low dose IL-2-induced NK and LAK cell activity, and increased the BL-esterase activity induced by high or low dose IL-2. The combination of IL-4 and IL-2 did not induce any large variation in the percentage of IL-2R (p55) expressing cells. In all tested conditions, IL-2R (p55) was mainly expressed on CD4+ T cells; less than 2% of the cells coexpressed the NK cell marker CD56 and IL-2R (p55). The effect of IL-4 upon IL-2-induced LAK cell expansion is thus very different on PBMC pre-activated in vivo by alpha IFN + IL-2 therapy than on PBMC pre-treated in vitro with IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Favrot
M
M
Centre Léon Bérard, Lyon, France.
Capdeville
R
R
Combaret
V
V
Zhou
D C
DC
Clapisson
G
G
Banchereau
J
J
Franks
C R
CR
Chouaib
S
S
Blay
J Y
JY
Philip
T
T
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D002478:Cells, Cultured; D004347:Drug Interactions; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000008:administration & dosage / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects
D007155:Immunologic Factors; D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins; D015847:Interleukin-4