PMID- 9862675 OWN - NLM STAT- MEDLINE DCOM- 19990122 LR - 20211025 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 161 IP - 12 DP - 1998 Dec 15 TI - Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. PG - 6510-7 AB - Ox-40 and Ox-40 ligand (Ox-40L) are thought to be involved in T cell-APC interactions. However, their exact role in T cell responses is undefined. Using fibroblast transfectants expressing Ox-40L and/or B7-1, and CD4 cells from TCR transgenic mice, we investigated the effect of Ox-40 signaling on primary responses to the Ag pigeon cytochrome c. Ox-40 expression on naive CD4 cells peaked 2 to 3 days after activation, and was lost by 4 to 5 days. APCs with Ox-40L promoted partial activation of naive T cells with some IL-2 secretion, but were unable to enhance proliferation, unlike those with B7-1. APCs coexpressing Ox-40L with B7-1 induced large quantities of IL-2 and promoted proliferative responses that persisted for several days. Effector cells taken 5 days after naive T cell activation reexpressed Ox-40 within 4 h and responded strongly to APCs expressing Ox-40L, whereas B7-1 had little effect. Synergy was also seen between Ox-40L and B7-1, with primarily IL-2 being elevated, although IL-4 and IL-5 were also up-regulated. The most striking action was on effector T cell proliferation, which continued at high levels for up to 4 days, with little proliferation evident at this time in the absence of Ox-40 signals. These data suggest that Ox-40/Ox-40L interactions act after initial activation events to prolong clonal expansion and enhance effector cytokine secretion, and may be involved in promoting long-lived primary CD4 responses. FAU - Gramaglia, I AU - Gramaglia I AD - Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. FAU - Weinberg, A D AU - Weinberg AD FAU - Lemon, M AU - Lemon M FAU - Croft, M AU - Croft M LA - eng GR - AI36259/AI/NIAID NIH HHS/United States GR - NS35421/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (B7-1 Antigen) RN - 0 (CD28 Antigens) RN - 0 (Cytochrome c Group) RN - 0 (Interleukin-2) RN - 0 (Interleukin-5) RN - 0 (Membrane Glycoproteins) RN - 0 (OX40 Ligand) RN - 0 (Peptide Fragments) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Receptors, OX40) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Tnfrsf4 protein, mouse) RN - 0 (Tnfsf4 protein, mouse) RN - 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7) RN - 0 (Tumor Necrosis Factors) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Animals MH - Antigen-Presenting Cells/*immunology MH - B7-1 Antigen/genetics/immunology MH - CD28 Antigens/immunology MH - CD4-Positive T-Lymphocytes/*immunology/metabolism MH - Cells, Cultured MH - Columbidae MH - Cytochrome c Group/immunology MH - Fibroblasts MH - Interleukin-2/metabolism MH - Interleukin-4/metabolism MH - Interleukin-5/metabolism MH - Lymphocyte Activation/*physiology MH - *Membrane Glycoproteins MH - Mice MH - Mice, Transgenic MH - OX40 Ligand MH - Peptide Fragments/immunology MH - Receptors, Antigen, T-Cell/genetics MH - Receptors, OX40 MH - Receptors, Tumor Necrosis Factor/genetics/*immunology MH - Recombinant Fusion Proteins/immunology MH - Transfection MH - Tumor Necrosis Factor Receptor Superfamily, Member 7/*immunology MH - Tumor Necrosis Factors EDAT- 1998/12/23 00:00 MHDA- 1998/12/23 00:01 CRDT- 1998/12/23 00:00 PHST- 1998/12/23 00:00 [pubmed] PHST- 1998/12/23 00:01 [medline] PHST- 1998/12/23 00:00 [entrez] PST - ppublish SO - J Immunol. 1998 Dec 15;161(12):6510-7.