Strong induction of ICAM‐1 in human T cells transformed by human T‐cell‐leukemia virus type 1 and depression of ICAM‐1 or LFA‐1 in adult T‐cell‐leukemia‐derived cell lines

Abstract

Sixteen human T-cell lines were studied for the expression of a cell-adhesion molecule ICAM-1 and its counter-receptor LFA-1. The cell lines included 3 human T-cell-leukemia-virus-type-I (HTLV-1)-negative cell lines derived from acute lymphoblastic leukemia (ALL) and 13 HTLV-1-positive cell lines, 7 of them established from cord- or peripheral-blood T cells by in vitro transformation with HTLV-1, 2 derived from HTLV-1 carriers, and 4 derived from patients with adult T-cell leukemia (ATL). In sharp contrast to a basal level of ICAM-1 in 3 HTLV-1-negative ALL cell lines, strong induction of ICAM-1 was seen in all HTLV-1-positive T-cell lines except for MT-1, one of the 4 ATL cell lines used in the present study. On the other hand, the expression of LFA-1 (CD11a and CD18) was more or less similar among the cell lines with and without HTLV-1. Interestingly, however, 3 out of 4 ATL cell lines (TL-Om1, H582, HUT102) revealed striking depression of LFA-1 expression. Several lines of evidence strongly argued against direct involvement of the viral transactivator p40tax or some autocrine cytokines in the induction of ICAM-1 in HTLV-1-positive T-cell lines. It was also found that ICAM-1 and LFA-1 were involved in syncytium formation induced in the co-culture of HTLV-1-positive and HTLV-1-negative human T-cell lines. Implications of constitutive expression of ICAM-1 for certain clinical manifestations of ATL and of depression of either ICAM-1 or LFA-1 during progression of ATL are discussed.

Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines

“…We know that KAI1 is a glycoprotein from studies of the protein in other contexts, C33, IA4 and 4F9 antigens, mainly in lymphocytes (Fukudome et al, 1992;Lebel-Binay et al, 1994;Nojima et al, 1993). The heterogeneous molecular weight, 42 ± 100 kD, of KAI1 in normal and malignant B and T cells is attributed to N-linked glycosylation in those studies.…”

“…KAI1 is identical to the previously characterized antigens R2, IA4, C33 and 4F9 and is designated CD82 by the clusters of dierentiation (CD) nomenclature (Engel and Tedder, 1994). KAI1(CD82) contains three potential N-linked glycosylation sites and is a glycoprotein (Dong et al, 1995;Fukudome et al, 1992;Lebel-Binay et al, 1994;Nojima et al, 1993). TM4SF proteins associate with each other and with other proteins such as CD4, CD8, Leu-13, CD19, CD20 and integrins (Angelisova et al, 1994;Berditchevski et al, 1996;Rubinstein et al, 1996;.…”

“…The study also showed that KAI1 mRNA expression is downregulated in human cell lines derived from prostate cancer metastases when compared to normal prostate cells, suggesting a suppressor role for KAI1 in human prostate cancer. KAI1 is ubiquitously expressed by human lymphoid and epithelial cells, and also is expressed by some ®broblasts (Dong et al, 1995;Fukudome et al, 1992). Therefore, it is possible that KAI1 is a metastasis suppressor gene for dierent types of human cancers.…”

Monographs on the Evaluation of Carcinogenic Risks to Humans

“…NK-cell activity as weIl as CTL activity (see Section 4.2.3) may play an important role in !imiting the expansion of HTL V-I-infected T-cells at this stage, and progression to A TLL requires a number of additional events. Whereas HTL V -1 producer T -cell lines express high levels of the adhesion molecules LF A -1, LF A -3 and ICAM -1, A TLL-deri ved cell 1ines show reduced expression of these surface markers (Fukudome et al, 1992) (Gazzolo & Duc Dodon, 1987;Duc Dodon et al, 1989), but the interpretation of this phenomenon remains controversiaI. Recombinant HTL V -1 envelope protein, expressed in a vaccinia virus vector (Cassé et al, 1994) does not induce T-cell proliferation.…”

“…Several adhesion molecules, such as LFA-3, ICAM-1, LFA-l, and the cell surface markers CD28, CD69 and CD5 show increased expression on the surface of HTL V -1-infected (Fukudome et al, 1992;Imai et al 1993) or tax-transfected (Ch1ichlia et al, 1995Tanaka et al, 1995) cells. Antibodies to CD2 and LFA-3 inhibit the mitogenic activity of HTLV-I-infected T-celllines (Kimata et al, 1993) and the spontaneous proliferation of PBMCs from HTL V -I-infected asymptomatic carriers or TSP/HAM patients (Höllsberg et al, 1992;Wucherpfennig et al, 1992), suggesting that these molecules contribute to the process of proliferation.…”