Requirements for the functional expression of OX40 ligand on human activated CD4+ and CD8+ T cells.
Interaction between OX40 expressed on activated T cells and its ligand (OX40L) on antigen presenting cells (APC) provides a co-stimulatory signal for T cells to promote acquired immunity. In the present study, we have examined various culture conditions for optimum OX40L expression on T cells stimulated with immobilized anti-CD3/CD28 monoclonal antibodies (mAbs). Although the day 3 primed T cells expressed minimal OX40L, after repeated stimulations both the CD4+ and CD8+ T cells became OX40L positive as determined by flow cytometry. Interleukin (IL)-12 interfered with the OX40L expression. Among activated T cells, a higher frequency of CD8+ T cells expressed OX40L than CD4+ T cells. By blocking OX40L-OX40 interaction by an anti-OX40 mAb, the number of OX40L+ T cells significantly increased. Screening of various cytokines showed that transforming growth factor (TGF)-beta1 was capable of induction of OX40L on the activated T cells within 3 days. The OX40L expressed on T cells was functional, as they bound soluble OX40 and stimulated human immunodeficiency virus-1 (HIV-1) production from cell lines chronically infected with HIV-1 and expressing OX40. Altogether the present study findings indicate that functional OX40L is inducible on human activated CD4+ and CD8+ T cells, and that the expression is enhanced by TGF-beta1.
Kondo
Kayo
K
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Okuma
Kazu
K
Tanaka
Reiko
R
Zhang
Li Feng
LF
Kodama
Akira
A
Takahashi
Yoshiaki
Y
Yamamoto
Naoki
N
Ansari
Aftab A
AA
Tanaka
Yuetsu
Y
D000911:Antibodies, Monoclonal / Q000009:adverse effects; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018929:Cell Culture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D053278:OX40 Ligand / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D053262:Receptors, OX40 / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D053278:OX40 Ligand; D053262:Receptors, OX40; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1