Comparison of OX40 Ligand and CD70 in the Promotion of CD4+ T Cell Responses.
Summary of "Comparison of OX40 Ligand and CD70 in the Promotion of CD4+ T Cell Responses."
The TNF superfamily members CD70 and OX40 ligand (OX40L) were reported to be important for CD4(+) T cell expansion and differentiation. However, the relative contribution of these costimulatory signals in driving CD4(+) T cell responses has not been addressed. In this study, we found that OX40L is a more important determinant than CD70 of the primary CD4(+) T cell response to multiple immunization regimens. Despite the ability of a combined TLR and CD40 agonist (TLR/CD40) stimulus to provoke appreciable expression of CD70 and OX40L on CD8(+) dendritic cells, resulting CD4(+) T cell responses were substantially reduced by Ab blockade of OX40L and, to a lesser degree, CD70. In contrast, the CD8(+) T cell responses to combined TLR/CD40 immunization were exclusively dependent on CD70. These requirements for CD4(+) and CD8(+) T cell activation were not limited to the use of combined TLR/CD40 immunization, because vaccinia virus challenge elicited primarily OX40L-dependent CD4 responses and exclusively CD70-dependent CD8(+) T cell responses. Attenuation of CD4(+) T cell priming induced by OX40L blockade was independent of signaling through the IL-12R, but it was reduced further by coblockade of CD70. Thus, costimulation by CD70 or OX40L seems to be necessary for primary CD4(+) T cell responses to multiple forms of immunization, and each may make independent contributions to CD4(+) T cell priming.
Integrated Department of Immunology, University of Colorado Denver and.
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20639485
- DOI: http://dx.doi.org/10.4049/jimmunol.1000172
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Medical and Biotech [MESH] Definitions
A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.
A tumor necrosis family receptor with specificity for OX40 LIGAND. It is found on the surface of activated T-LYMPHOCYTES where it plays a role in enhancing cytokine production and proliferation of CD4-POSITIVE T-LYMPHOCYTES. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Comparison of outcomes, results, responses, etc for different techniques, therapeutic approaches or other inputs.
Comparison of various psychological, sociological, or cultural factors in order to assess the similarities or diversities occurring in two or more different cultures or societies.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.