OX40-OX40 Ligand Interaction through T Cell-T Cell Contact Contributes to CD4 T Cell Longevity
| Autor: | Naoto Ishii, Kazuo Sugamura, Pejman Soroosh, Shouji Ine |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Time Factors Cell Survival T cell Immunology Down-Regulation Mice Transgenic OX40 Ligand Cell Communication Biology Lymphocyte Activation Receptors Tumor Necrosis Factor Mice Interleukin 21 Cell Line Tumor medicine Animals Immunology and Allergy Cytotoxic T cell IL-2 receptor Antigen-presenting cell Cells Cultured Cell Proliferation Mice Knockout Membrane Glycoproteins ZAP70 CD28 Receptors OX40 Natural killer T cell Cell biology Mice Inbred C57BL medicine.anatomical_structure Tumor Necrosis Factors Female Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.176.10.5975 |
| Popis: | Signals through the OX40 costimulatory receptor on naive CD4 T cells are essential for full-fledged CD4 T cell activation and the generation of CD4 memory T cells. Because the ligand for OX40 is mainly expressed by APCs, including activated B cells, dendritic cells, and Langerhans cells, the OX40-OX40 ligand (OX40L) interaction has been thought to participate in T cell-APC interactions. Although several reports have revealed the expression of OX40L on T cells, the functional significance of its expression on them is still unclear. In this study, we demonstrate that Ag stimulation induced an increase in the surface expression and transcript levels of OX40L in CD4 T cells. Upon contact with OX40-expressing T cells, the cell surface expression of OX40L on CD4 T cells was markedly down-regulated, suggesting that OX40-OX40L binding occurs through a novel T cell-T cell interaction. To investigate the function of this phenomenon, we examined the proliferative response and survival of OX40L-deficient CD4 T cells when challenged with Ag. In vitro studies demonstrated markedly less CD3-induced proliferation of OX40L-deficient CD4 T cells compared with wild-type CD4 T cells. When using TCR transgenic CD4 T cells upon Ag stimulation, survival of OX40L-deficient T cells was impaired. Furthermore, we show that upon antigenic stimulation, fewer OX40L-deficient CD4 T cells than wild-type cells survived following transfer into wild-type and sublethally irradiated recipient mice. Taken together, our findings indicate that OX40L-expressing T cells have an autonomous machinery that provides OX40 signals through a T cell-T cell circuit, creating an additional mechanism for sustaining CD4 T cell longevity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|