Expression and function of insulin-like growth factor receptors on anti-CD3-activated human T lymphocytes.
The pattern of expression of receptors for insulin-like growth factors (IGF-I and IGF-II) and insulin was studied on monocyte-depleted human peripheral blood T cells activated via anti-CD3. Binding assays demonstrated the sequential appearance of receptors for IGF-I, IGF-II, and insulin on activated T cells. IGF-IR appeared early, their expression reaching maximum levels at or before the peak of cellular proliferation. IGF-IIR expression generally followed that of the IGF-IR and was more transient, with increases and decreases in expression paralleling the rise and decline of cellular proliferation. Insulin receptor expression remained low throughout the activation time course. The identity of the IGFR on anti-CD3-activated T cells was confirmed in affinity cross-linking experiments. These data demonstrated a 135,000 Mr peptide that specifically binds radiolabeled IGF-I and corresponds to the alpha subunit of the type I IGF-IR, and a 260,000 Mr peptide that specifically binds radiolabeled IGF-II and corresponds to the type II IGFR. We have additionally found that IGF-I and IGF-II (in nanomolar concentrations) produce as much as a threefold enhancement of T cell proliferation early in the activation process, correlating with the early appearance of IGF-IR. The effect of both IGF appeared to be mediated through the type I receptor, since an antibody (alpha IR3), which blocks binding to the alpha subunit of this receptor, inhibited enhancement by up to 83%. Furthermore, we have found expression of IGF-IR on T cells after activation to be associated with both CD4+ and CD8+ T cell subpopulations. These observations provide a foundation for investigating the contribution of IGF in regulating T cell proliferation, differentiation, and effector function.
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
E W
EW
Johnson
L A
LA
Jones
R W
RW
Kozak
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016827:CD8 Antigens / Q000032:analysis; D003432:Cross-Linking Reagents; D016895:Culture Media, Serum-Free; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D011940:Receptor Aggregation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D017451:Receptors, Somatomedin; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D016895:Culture Media, Serum-Free; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II