IL-1 and IL-4 as reciprocal regulators of IL-2 induced lymphocyte cytotoxicity.
Interleukin 4 (IL-4) suppresses the interleukin 2 (IL-2) induced lymphokine-activated killer (LAK) cell development from human peripheral blood mononuclear cells (PBMC). Suppression is observed at high (1,000 U ml-1) as well as low (10 U ml-1) concentrations of IL-2. IL-4 needs to be present at the beginning of the IL-2 culture to exert the suppressive effect. IL-4 also inhibits the development of CD25 (Tac) antigen on the PBMC cultured in IL-2. Interleukin 1 (IL-1) can reverse the suppressive effect of IL-4 on LAK induction when added at the early phase of the IL-2 culture. IL-1 enhances IL-2 induced LAK development, which may partially explain the reversion of IL-4 inhibition by IL-1. IL-1 also reverses the inhibitory effect of IL-4 on the development of CD25 antigen expression, although IL-1 alone does not enhance the induction of CD25 expression in PBMC cultured by IL-2. Furthermore, IL-4 suppresses IL-2 induced IL-1 production in PBMC. Thus, suppression of CD25 may be a pathway for the suppression of LAK induction. The expression of CD56 is not directly associated with the expression of LAK activity. IL-4, IL-1 or combination of the two cytokines has no effect on IL-2 induced expression of CD56. These results indicate that IL-4 has an antagonistic effect and IL-1 has a synergistic effect on IL-2-induced LAK development.
Department of Surgery, UCLA School of Medicine 90024-1782.
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N
Ebina
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D
Gallardo
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H
Shau
S H
SH
Golub
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D019002:CD56 Antigen; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000032:analysis
D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D007375:Interleukin-1; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4