Regulation of the cell-surface expression of an HTLV-I binding protein in human T cells during immune activation

Abstract

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) immu-noadhesin, 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 immu-noadhesin 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 immuno-biology of CD4 T cells. (Blood. 2003;101: 3085-3092)

Cell Surface Expression of the Bovine Leukemia Virus-Binding Receptor on B and T Lymphocytes Is Induced by Receptor Engagement

“…The characteristics of BLV expression on lymphocyte subsets are evocative of that previously reported for the HTLV receptor (28,44). Indeed, even before this receptor was identified as the Glut1 glucose transporter, it had been determined that Glut1 expression is closely linked to the metabolic state of the lymphocyte (50 -53).…”

“…4A), a T cell survival factor that can stimulate proliferation of these T cells without inducing an extensive activation profile (42,43). These data are very reminiscent of the expression profile of the HTLV receptor Glut1 (29,44) and indicate that the BLV Env-binding receptor is a novel cell cycle entry/proliferation marker in both B and T lymphocytes.…”

HTLV-1 tropism and envelope receptor

“…Indeed, as we and others reported for the as yet unknown HTLV receptor, GLUT1 is not detectable on resting lymphocytes and is a major marker of active lymphocyte metabolism (Chakrabarti et al, 1994;Frauwirth et al, 2002). Moreover, TCR engagement of naı¨ve and memory T cells (Manel et al, 2003b;Nath et al, 2003) and TGF-b-induced signaling of neonatal T lymphocytes rapidly induce GLUT1 expression at the cell surface, as measured with HTLV SU-derived ligands. Finally, it is notable that the homeostatic cytokine IL-7 induces surface GLUT1 expression on neonatal T cells to a significantly higher level than on adult T cells, as assessed by HRBD binding.…”

“…Indeed, we (Manel et al, 2003b), using HRBD constructs, and others using an entire SU (Nath et al, 2003), observed no or little expression of the HTLV Env receptor in freshly isolated peripheral blood mononuclear cells, including CD4 þ T cells. This a priori puzzling result was elucidated by the observation that T-cell receptor activation of both memory and naı¨ve T cells led to the rapid emergence, within 4-6 h, of cell surface HTLV receptor expression on CD4 þ as well as CD8 þ T lymphocytes (Manel et al, 2003b;Nath et al, 2003). Therefore, increased expression of the receptor at cell surface is an early marker of T lymphocyte activation, a feature that has most likely contributed to the receptor selection by HTLV.…”

“…Therefore, increased expression of the receptor at cell surface is an early marker of T lymphocyte activation, a feature that has most likely contributed to the receptor selection by HTLV. Moreover, in vitro activation of other hematopoietic populations was also associated with an HTLV receptor upregulation (Nath et al, 2003).…”