A soluble 'anchorminus' interleukin 2 receptor suppresses in vitro interleukin 2-mediated immune responses.
The immunosuppressive effects of a recombinant soluble IL-2 receptor L chain (s-IL-2R) were analyzed. S-IL-2R protein was obtained from the conditioned medium of L cells transfected with a mutant cDNA clone encoding the extracytoplasmic portion of the IL-2 receptor (IL-2R) and was purified to homogeneity by an IL-2-coupled sepharose column, following by reverse phase chromatography (HPLC). Soluble IL-2R protein thus prepared retained the ability to bind IL-2 specifically and suppressed the in vitro IL-2-mediated immune responses, including proliferation of IL-2-dependent cell line (CTLL-2), induction of secondary cytotoxic T lymphocytes (CTL) and the mixed lymphocyte reaction (MLR), but did not suppress the growth of IL-3-dependent cell line. Kinetic studies revealed that s-IL-2R exhibited the suppressive effects on the proliferative responses of alloantigen stimulated human tonsillar cells, only when added at an early stage, namely 0-48 h after culture onset, whereas cyclosporin A (CsA) exhibited an inhibitory effect only when added at between 0 and 24 h. This implies that s-IL-2R exerts its effect on an early stage of lymphocyte activation. The observed immunosuppressive effects of s-IL-2R suggest the possibility that s-IL-2R might be useful for the protection of rejection crisis in organ transplantation.
Kondo
N
N
Central Research Laboratories, Ajinomoto Co. Inc., Kawasaki, Japan.
Kondo
S
S
Shimizu
A
A
Honjo
T
T
Hamuro
J
J
D000818:Animals; D002460:Cell Line; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification*; D007376:Interleukin-2 / Q000276:immunology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D015375:Receptors, Interleukin-2 / Q000276:immunology* / Q000302:isolation & purification; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2