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.
Affiliation
Integrated Department of Immunology, University of Colorado Denver and.
Journal Details
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20639485
- DOI: http://dx.doi.org/10.4049/jimmunol.1000172
Medical and Biotech [MESH] Definitions
Ox40 Ligand
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.
Receptors, Ox40
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.
Comparative Study
Comparison of outcomes, results, responses, etc for different techniques, therapeutic approaches or other inputs.
Cross-cultural Comparison
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.
Receptors, Tnf-related Apoptosis-inducing Ligand
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.
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