The related cytokines interleukin-13 and interleukin-4 are distinguished by differential production and differential effects on T lymphocytes.
We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium. Certain inducing combinations such as PMA and anti-CD28, stimulate high levels of IL-13 and IL-13 mRNA, but little or no IL-4 or IL-4 mRNA. The ratio of IL-13 to IL-4, both at protein and mRNA levels, is higher in CD8+ lymphocyte than in CD4+ lymphocyte populations. Although after in vitro polarization of peripheral blood lymphocytes leading to type 1 and type 2 populations, IL-13 is made principally by cells of a type 2 phenotype, as is IL-4; it can also be produced by type 1 CD4+ and CD8+ T lymphocyte clones making large amounts of IFN-gamma and very little IL-4. IL-13 and IL-4 exert different effects on T lymphocyte functions. IL-13 does not significantly inhibit the IL-2-induced T lymphocyte production of IFN-gamma, RANTES, MIP-1 alpha or MIP-1 beta, nor that of perforin mRNA, as does IL-4. We have also been unable to demonstrate STAT6 activation by IL-13 on T lymphocytes purified in a number of ways, despite strong activation of STAT6 by IL-4 in these cells. This is contrary to some previous reports, but is consistent with the notion that the majority of T lymphocytes lack functional IL-13 receptors. A higher and more prolonged T lymphocyte production of IL-13 than that of IL-4 may thus be permissible because IL-13 does not inhibit T-cell functions. Conversely, sustained IL-13 production may be partly due to the absence of receptor-mediated depletion of this cytokine.
Minty
A
A
Sanofi Recherche, Labège-Innopole, France. adrian.minty@tis1.elfsanofi.fr
Asselin
S
S
Bensussan
A
A
Shire
D
D
Vita
N
N
Vyakarnam
A
A
Wijdenes
J
J
Ferrara
P
P
Caput
D
D
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D017931:DNA Primers; D018793:Interleukin-13; D012333:RNA, Messenger; D015847:Interleukin-4