Functional CD4 T cells after intercellular molecular transfer of 0X40 ligand.
OX40/OX40 ligand (OX40L) proteins play critical roles in the T cell-B cell and T cell-dendritic cell interactions. Here we describe the intercellular transfer of OX40L molecules by a non-Ag specific manner. After 2-h coculture of activated CD4(+) T cell (OX40L(-), OX40(+)) with FLAG peptide-tagged OX40L (OX40L-flag) protein-expressing COS-1 cells, the OX40L-flag protein was detected on the cell surface of the CD4(+) T cells by both anti-OX40L and anti-FLAG mAbs. The intercellular OX40L transfer was specifically abrogated by pretreatment of the COS-1 cells with anti-OX40L mAb, 5A8. The OX40L transfer to OX40-negative cells was also observed, indicating an OX40-independent pathway of OX40L transfer. HUVECs, allostimulated monocytes, and human T cell leukemia virus type I-infected T cells, which all express OX40L, can potentially act as the donor cells of OX40L. The entire molecule of OX40L was transferred and stabilized on the recipient cell membrane with discrete punctate formation. The transferred OX40L on normal CD4(+) T cells was functionally active as they stimulated latent HIV-1-infected cells to produce viral proteins via OX40 signaling. Therefore, these findings suggest that the intercellular molecular transfer of functional OX40L may be involved in modifying the immune responses.
Baba
E
E
Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan. e-baba@tumor.med.kyushu-u. ac.jp
Takahashi
Y
Y
Lichtenfeld
J
J
Tanaka
R
R
Yoshida
A
A
Sugamura
K
K
Yamamoto
N
N
Tanaka
Y
Y
D000818:Animals; D019921:Biotinylation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019556:COS Cells; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D018920:Coculture Techniques; D005110:Extracellular Space / Q000276:immunology* / Q000378:metabolism*; D006367:HeLa Cells; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053278:OX40 Ligand; D009842:Oligopeptides; D010455:Peptides / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D008024:Ligands; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D009842:Oligopeptides; D010455:Peptides; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C089251:TNFSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C085706:FLAG peptide