A monoclonal antibody to the T-cell receptor increases IGF-I receptor content in normal T-lymphocytes: comparison with phytohemagglutinin.
The biological effects of the IGFs are mediated through interaction with specific cell surface receptors. It has been previously reported that mitogenic activation of T-lymphocytes by phytohemagglutinin (PHA) is associated with increased IGF-I receptor content. However, the mechanisms which regulate IGF-I receptor expression during T-lymphocyte activation are unknown. To explore further the regulation of IGF-I receptor expression in T-cells, we investigated IGF-I receptor content and mRNA abundance in T-lymphocytes after stimulation either by PHA or OKT-3, the latter being a monoclonal antibody directed against the CD-3 antigen of the T-cell receptor. IGF-I binding in T-cells demonstrated increased IGF-I receptor content after stimulation by both PHA and OKT-3. Peak binding was induced after 72 h of treatment with PHA and 48 h of treatment with OKT-3. Affinity cross-linking of 125I-IGF-I to T-cell membranes demonstrated a single approximately 130 kDa band which was increased after treatment with PHA or OKT-3. This band was inhibited by the addition of alpha-IR3, a monoclonal antibody to the IGF-I receptor. Both PHA and OKT-3 increased IGF-I receptor mRNA abundance with peak increases at 20 h and 60 h, respectively. Parallel increases in IGF-I receptor and beta-actin mRNA abundance were observed, consistent with previous studies demonstrating increased actin gene expression after T-cell activation. Thus, the increase in IGF-I receptor mRNA abundance markedly preceded the increase in IGF-I receptor content after PHA stimulation, but the increase in IGF-I receptor mRNA abundance followed the increase in IGF-I receptor content after OKT-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Hartmann
K K
KK
Division of Diabetes and Endocrine Research, Mount Zion Medical Center, University of California, San Francisco 94120.
Baier
T G
TG
Papa
V
V
Kronenwett
M
M
Brown
E J
EJ
Goldfine
I D
ID
Rosenthal
S M
SM
D000199:Actins / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D015870:Gene Expression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008213:Lymphocyte Activation; D016853:Muromonab-CD3 / Q000276:immunology*; D010835:Phytohemagglutinins; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000199:Actins; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016853:Muromonab-CD3; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I