Fas Ligand Costimulates the In Vivo Proliferation of CD8+ T Cells

• Published in: The Journal of immunology (1950) 2000-11, Vol.165 (10), p.5537-5543
• Main Authors: Suzuki, Ivy, Martin, Stefan, Boursalian, Tamar E, Beers, Courtney, Fink, Pamela J
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Apoptosis - genetics; Apoptosis - immunology; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - transplantation; Cell Size - immunology; Clone Cells; Cytotoxicity, Immunologic - genetics; Epitopes, T-Lymphocyte - metabolism; Fas Ligand Protein; fas Receptor - metabolism; Injections, Intravenous; Ligands; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocyte Count; Lymphocyte Transfusion; Membrane Glycoproteins - administration & dosage; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - physiology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Mice, Transgenic; Species Specificity
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.10.5537

Fas ligand (FasL/CD95L/APO-1L) is one of a growing number of TNF family members whose triggering costimulates maximal proliferation of activated T cells. In this study we show that maximal Ag-dependent accumulation of transferred TCR-transgenic CD8(+) T cells requires Fas (CD95/APO-1) expression by the adoptive hosts. Additionally, adoptively transferred FasL(+) CD8(+) T cells demonstrate a 2-fold advantage in Ag-driven expansion over their FasL(-)counterparts. This study illustrates the in vivo role of TCR-dependent FasL costimulation in the Ag-specific proliferation of both heterogeneous and homogeneous populations of primary CD8(+) T cells and long-term CTL lines. Thus, cross-linking FasL on naive and Ag-experienced CD8(+) T cells whose Ag-specific TCRs are engaged is required to drive maximal cellular proliferation in vivo.