Lymphocyte transformation and thiol compounds; the role of ADF/thioredoxin as an endogenous reducing agent.
ADF (adult T-cell leukemia-derived factor), an inducer of IL-2R with growth promoting activity, is a homologue of thioredoxin which is involved in many thiol-dependent reducing reactions. ADF is constitutively produced and released by human lymphoid cell lines transformed by lymphocyte-tropic viruses, such as human T-lymphotropic virus type I (HTLV-I) and Epstein-Barr virus (EBV). We found that the viability and growth of these ADF high-producer cell lines (ATL-2, HUT102, MT-2, 3B6 and RPM18866) were highly dependent on L-cystine in the culture. In contrast to the relative cystine independency of ADF low-producer cells (Jurkat, Jijoye, U937 and K562), the growth of ADF high-producer cells was almost completely suppressed in L-cystine-free condition. Their viability and growth in L-cystine-free medium were markedly improved by 5 x 10(-5) M L-cysteine, 5 x 10(-5) M 2-ME or 10(-3) M GSH and partially by 10(-3) M DTT. The results demonstrate the requirement of reducing condition involving thiol compounds for the optimal growth of the virally transformed lymphoid cells. Furthermore, recombinant ADF (rADF) and suboptimal dose of 2-ME additively enhanced the growth of ATL-2 cells in L-cystine-free medium, implying the possible involvement of endogenous reducing agents such as ADF/thioredoxin homologue in the process of lymphocyte transformation/activation.
Yamauchi
A
A
Second Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Masutani
H
H
Tagaya
Y
Y
Wakasugi
N
N
Mitsui
A
A
Nakamura
H
H
Inamoto
T
T
Ozawa
K
K
Yodoi
J
J
D002460:Cell Line; D003553:Cystine / Q000378:metabolism / Q000494:pharmacology; D006133:Growth Substances / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008221:Lymphoid Tissue / Q000166:cytology; D008623:Mercaptoethanol / Q000494:pharmacology; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D013879:Thioredoxins / Q000378:metabolism
D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; C047526:leukemia growth-promoting factor; D003553:Cystine; D013879:Thioredoxins; D008623:Mercaptoethanol