Regulation of the cell-surface expression of an HTLV-I binding protein in human T cells during immune activation.
Little is known about the requirements for human T-cell leukemia virus type I (HTLV-I) entry, including the identity of the cellular receptor(s). Recently, we have generated an HTLV-I surface glycoprotein (SU) immunoadhesin, HTSU-IgG, which binds specifically to cell-surface protein(s) critical for HTLV-I-mediated entry in cell lines. Here, expression of the HTLV-I SU binding protein on primary cells of the immune system was examined. The immunoadhesin specifically bound to adult T cells, B cells, NK cells, and macrophages. Cell stimulation dramatically increased the amount of binding, with the highest levels of binding on CD4(+) and CD8(+) T cells. Naive (CD45RA(high), CD62L(high)) CD4(+) T cells derived from cord blood cells, in contrast to other primary cells and all cell lines examined, bound no detectable HTLV-I SU. However, following stimulation, the level of HTSU-IgG binding was rapidly induced (fewer than 6 hours), reaching the level of binding seen on adult CD4(+) T cells by 72 hours. In contrast to HTLV-I virions, the soluble HTSU-IgG did not effect T-cell activation or proliferation. When incubated with human peripheral blood mononuclear cells in a mixed leukocyte reaction, HTSU-IgG inhibited proliferation at less than 1 ng/mL. These results indicate that cell-surface expression of the HTLV SU binding protein is up-regulated during in vitro activation and suggest a role for the HTLV-I SU binding proteins in the immunobiology of CD4(+) T cells.
Nath
Manisha D
MD
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, MD 21702, USA.
Ruscetti
Francis W
FW
Petrow-Sadowski
Cari
C
Jones
Kathryn S
KS
D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007694:Killer Cells, Natural / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000378:metabolism; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000276:immunology
C080823:HTLV-I receptor; D007074:Immunoglobulin G; D011991:Receptors, Virus