| Abstract: |
We used an in vitro T-lymphoblast clonal proliferation assay to quantify human IGF-I (hIGF-I)-, human PTH (hPTH)-, human ACTH (hACTH)-, and human TSH (hTSH)-stimulated growth of human T-cell leukemia virus-II-transformed T-lymphoblast cell lines from normal individuals and to elucidate the role of IGF-I as the mediator of hPTH-, hACTH-, and hTSH-induced T-cell growth. Normal T-lymphoblast cell lines respond to hIGF-I in a bimodal fashion. The mean first peak response was 143 ± 9.8% above baseline (defined as 100%) occurring at 8 μg/L, and the mean second peak response was 154 ± 14.4% occurring at 100 μg/L. Both responses were completely blocked after incubation with aIR-3, an MAb to the IGF-I receptor (by analysis of variance, p = 0.015 between full response curves). After stimulation with hPTH, the mean peak clonal response of normal T-lymphoblast cell lines was 189 ± 7.0%; after incubation with odR-3, the mean peak clonal response was 108 ± 7.9% (p = 0.0015 between full response curves). The mean peak clonal response of normal T-lymphoblast cell lines after hACTH stimulation was 192 ± 8.6%; preincubation with aIR-3 reduced the mean peak clonal response to 94 ± 1.2% (p < 0.0001 between full response curves). With hTSH stimulation, the mean peak clonal response of normal T-lymphoblast cell lines was 167 ± 7.0%; after incubation with aIR-3, the mean peak clonal response was 94 ± 8.2% (p = 0.003 between full response curves). After stimulation with hIGF-1, hPTH, hACTH, and hTSH, the mean peak clonal responses of a pygmy T-lymphoblast cell line were 112 ± 8.2, 122 ± 1.5, 99 ± 4.2, and 98 ± 5.5%, respectively (all p s 0.0004 between corresponding complete pygmy and normal response curves). These data indicate that hPTH, hACTH, and hTSH stimulate growth of normal human T-lymphoblast cell lines through local action of IGF-I, because these effects can all be blocked by preincubation with MAb against the IGF-I receptor. The pygmy T-lymphoblast cell line showed little or no clonal expansion in the presence of hIGF-I itself, or in response to hPTH, hACTH, or hTSH, further supporting the notion that an intact IGF-I response mechanism is necessary for the proliferative response to hPTH, hACTH, and hTSH in human T-lymphoblasts. © 1995 International Pediatric Research Foundation, Inc. |
| Keywords: |
adult; unclassified drug; human cell; cell proliferation; t-lymphocytes; reproducibility of results; cell division; cell growth; reference values; cell line, transformed; body height; somatomedin c; insulin-like growth factor i; recombinant thyrotropin; cell transformation, viral; thyrotropin; corticotropin; tetracosactide; parathyroid hormone[1-34]; human t-lymphotropic virus 2; parathyroid hormones; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; stimulation, chemical; t lymphoblast; negroid race
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