Induction of the expression of gag protein in HTLV-I infected lymphocytes by anti-ICAM 1 antibody in vitro
Introduction
The human T-cell leukemia virus I (HTLV-I) is known to be a causative agent of adult T-cell leukemia (ATL) (Yoshida et al., 1982) and HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (Roman and Osame, 1988).
Several phenomena regarding an abnormal immune response have been reported in HAM/TSP patients. They have a high titer of anti HTLV-I antibody in the serum and CSF, while demonstrating a rather low titer in ATL. The number of activated, helper/inducer T-cells also increase in the peripheral circulation of HAM/TSP patients (Itoyama et al., 1989). It is known that these lymphocytes start to proliferate spontaneously in an in vitro culture (spontaneous PBL proliferation) (Itoyama et al., 1988).
No detectable HTLV-I protein was expressed in the circulating peripheral blood lymphocytes of either HAM/TSP patients or healthy carriers, whereas only a small percentage of PBLs expressed HTLV-I protein after spontaneous proliferation in vitro.
Intercellular adhesion molecule, ICAM 1 and ICAM 2 are usually expressed at very low levels. ICAM 1 is rapidly upregulated by inflammatory cytokines. Recent reports have shown the increase in the expression of ICAM 1 in the HTLV-I infected cell lines as well as in the CD4+ T-cells of peripheral blood lymphocytes (PBLs) from HAM/TSP patients (Fukudome et al., 1992). We recently investigated the influence of stimulating anti-ICAM 1 antibody on the spontaneous proliferation of peripheral blood lymphocytes (PBLs) from HAM/TSP patients. We herein report that the stimulation of ICAM 1 with anti-ICAM 1 antibody induced the expression of HTLV-I protein in the PBLs of HAM/TSP patients in an in vitro culture.
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Cell lines and culture
The PBLs of HAM/TSP patients, HTLV-I carriers, adult T cell leukemia (ATL) and other neurological disease (OND) were isolated under sterile conditions by Ficoll gradient centrifugation and then were maintained in RPMI 1640, 10% heat-inactivated fetal calf serum, penicillin (100 IU/ml), streptomycin (100 mg/ml). The CD4+ T-cells were enriched from the PBLs of HAM/TSP patients using a CD4 Microselecterflask (AIS Microcellector). Immortalized cell lines, MOLT4, HSB2, K562, previously determined by
Flow cytometry analysis
In the flow cytometry analysis, HTLV-I negative cell lines expressed little ICAM1, on the other hand, HTLV-I infected T cell lines strongly expressed ICAM 1 molecule on their surface (Fig. 1). The percentage of ICAM 1 positive CD4+ T-cells was much higher in PBLs of HAM/TSP patients than in other neurological controls. The PBLs of the HTLV-I carriers and adult T-cell leukemia patients also had a moderate to high percentage of ICAM 1 positive CD4+ T-cells (Fig. 2). It is known that the
Discussion
Adhesion molecules play an important role in inflammatory reactions. Among them, ICAM 1, a ligand for the lymphocyte function-associated antigen (LFA1) of leukocytes, may be expressed by antigen-presenting cells and keratinocytes in various inflammatory disorders. The ICAM family consists of three members. All are ligands for LFA1, and ICAM 1 can also bind Mac1. The ICAMs are not functionally redundant, since they have quite distinct expression profiles and can bind to LFA1 differentially. ICAM
Acknowledgements
This work was supported in part by Grant in Aid from the Ministry of Education, Science and Culture of Japan.
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