Anti-TNFRSF25 (aa 1-200) polyclonal antibody

Background. Only a few infants develop acute bronchiolitis when exposed to respiratory syncytial virus (RSV), and host, environmental, and viral properties are probably all of importance in determining the severity of infection. Methods. Microarray analysis was used to identify differentially expressed single genes and gene sets in cord blood from 5 infants hospitalized with RSV bronchiolitis versus cord blood from 5 control infants exposed to RSV without bronchiolitis during infancy. Quantitative real-time polymerase chain reaction (QRT-PCR) was performed on single genes in both the 5 infants selected for microarray analysis and 13 more infants hospitalized with the same disease. Gene set enrichment analysis (GSEA) was performed to identify differentially expressed gene sets within the microarray experiments. Results. Microarray analysis identified 15 single genes to be significantly differentially expressed between case and control infants. Eleven of these genes were evaluated with QRT-PCR, and the genes FAM102A, TNFRSF25, and STMN3 were down-regulated in all but 1 of the 18 infants. A pathway involved in regulation of the actin cytoskeleton was found to be clearly down-regulated when analyzed with GSEA. Conclusions. FAM102A, TNFRSF25, and STMN3 and a pathway involved in regulation of the actin cytoskeleton are down-regulated in cord blood from infants hospitalized with RSV bronchiolitis.

TNFR superfamily (TNFRSF)4 (OX40, CD134) and TNFRSF25 are costimulatory receptors that influence CD4(+) and CD8(+) T cell responses to cognate Ag. Independently, these receptors have been described to stimulate overlapping functions, including enhanced proliferation and activation for both regulatory T cells (CD4(+)Foxp3(+); Tregs) and conventional T cells (CD4(+)Foxp3(-) or CD8(+)Foxp3(-); Tconvs). To determine the relative functionality of TNFRSF4 and TNFRSF25 in T cell immunity, the activity of TNFRSF4 and TNFRS25 agonistic Abs was compared in the context of both traditional protein/adjuvant (OVA/aluminum hydroxide) and CD8(+)-specific heat shock protein-based (gp96-Ig) vaccine approaches. These studies demonstrate that both TNFRSF4 and TNFRSF25 independently and additively costimulate vaccine-induced CD8(+) T cell proliferation following both primary and secondary Ag challenge. In contrast, the activities of TNFRSF4 and TNFRSF25 were observed to be divergent in the costimulation of CD4(+) T cell immunity. TNFRSF4 agonists were potent costimulators of OVA/aluminum hydroxide-induced CD4(+) Tconv proliferation, but they only weakly costimulated Treg proliferation and IgG2a production, whereas TNFRSF25 agonists were strong costimulators of Treg proliferation, producers of IgG1, IgG2a, and IgG2b, and weak costimulators of CD4(+) Tconv proliferation. Interestingly, Ag-specific cellular and humoral responses were uncoupled upon secondary immunization, which was dramatically affected by the presence of TNFRSF4 or TNFRSF25 costimulation. These studies highlight the overlapping but nonredundant activities of TNFRSF4 and TNFRSF25 in T cell immunity, which may guide the application of receptor agonistic agents as vaccine adjuvants for infectious disease and tumor immunity. The Journal of Immunology, 2012, 189: 3311-3318.