Natural OX40L expressed on human T cell leukemia virus type-I-immortalized T cell lines interferes with infection of activated peripheral blood mononuclear cells by CCR5-utilizing human immunodeficiency virus.
BACKGROUND
OX40 ligand (OX40L) co-stimulates and differentiates T cells via ligation of OX40 that is transiently induced on T cells upon activation, resulting in prolonged T cell survival and enhanced cytokine production by T cells. This view has led to the targeting of OX40 as a strategy to boost antigen specific T cells in the context of vaccination. In addition, the ligation of OX40 has also been shown to inhibit infection by CCR5-utilizing (R5) but not CXCR4-utilizing (X4) human immunodeficiency virus type-1 (HIV-1) via enhancement of production of CCR5-binding β-chemokines. It was reasoned that human T cell leukemia virus type-I (HTLV-1) immortalized T cell lines that express high levels of OX40L could serve as an unique source of physiologically functional OX40L. The fact that HTLV-1+ T cell lines simultaneously also express high levels of OX40 suggested a potential limitation.


RESULTS
Results of our studies showed that HTLV-1+ T cell lines bound exogenous OX40 but not OX40L, indicating that HTLV-1+ T cell lines express an active form of OX40L but an inactive form of OX40. Anti-OX40 non-blocking monoclonal antibody (mAb), but not blocking mAb, stained HTLV-1+ T cell lines, suggesting that the OX40 might be saturated with endogenous OX40L. Functionality of the OX40L was confirmed by the fact that a paraformaldehyde (PFA)-fixed HTLV-1+ T cell lines inhibited the infection of autologous activated peripheral blood mononuclear cells (PBMCs) with R5 HIV-1 which was reversed by either anti-OX40L blocking mAb or a mixture of neutralizing mAbs against CCR5-binding β-chemokines.


CONCLUSIONS
Altogether, these results demonstrated that autologous T cell lines immortalized by HTLV-1 can be utilized as a conventional source of physiologically functional OX40L.
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan. yuetsu@s4.dion.ne.jp.
Daigo
D
Kasahara
Azusa
A
Takara
Yoshiaki
Y
Takahashi
Akira
A
Kodama
Reiko
R
Tanaka
Aftab A
AA
Ansari
Yuetsu
Y
Tanaka
D002460:Cell Line; D002472:Cell Transformation, Viral; D015497:HIV-1 / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D053278:OX40 Ligand / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology*
C584933:CCR5 protein, human; D053278:OX40 Ligand; D019713:Receptors, CCR5; D015728:Receptors, HIV; C089251:TNFSF4 protein, human