Modulation of interleukin 2 internalization and interleukin 2-dependent cell growth by antireceptor antibodies.
The growth factor interleukin 2 (IL2) binds to and is internalized together with high-affinity surface receptors present on lymphoid cells. This endocytosis thus results in down-regulation of the receptors. However, it is not known if the internalization is relevant to the induction of cell growth. In the present study a rat monoclonal antibody to the P55 chain of the IL2 receptor was used to examine the role of receptor internalization in the IL2-dependent autocrine human tumor T cell line IARC 301. When given alone, this antibody did not inhibit IL2 binding, internalization, or IL2-dependent cell proliferation. However, crosslinking by anti-rat immunoglobulins, which did not affect binding of the growth factor, inhibited both IL2 internalization and cell proliferation. Besides offering a novel means for the specific inhibition of the uptake of IL2 bound to IL2 high-affinity receptors, the results are compatible with the association of this receptor-ligand uptake to the growth stimulation by IL2.
Duprez
V
V
Unité de Génétique Somatique (Centre National de la Recherche Scientifique URA 361), Institut Pasteur, Paris, France.
Ferrer
M
M
Cornet
V
V
Olive
D
D
Dautry-Varsat
A
A
D000911:Antibodies, Monoclonal; D002455:Cell Division; D002460:Cell Line; D015536:Down-Regulation; D004705:Endocytosis; D006801:Humans; D007152:Immunologic Capping; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology*; D011940:Receptor Aggregation; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D015375:Receptors, Interleukin-2