%0 Journal Article %J J Immunol %D 2004 %T 4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses. %A Dawicki, Wojciech %A Bertram, Edward M %A Sharpe, Arlene H %A Watts, Tania H %K 4-1BB Ligand %K Adoptive Transfer %K Animals %K Antigens, CD %K Antigens, CD137 %K CD4-Positive T-Lymphocytes %K CD8-Positive T-Lymphocytes %K Cell Proliferation %K Enterotoxins %K Epitopes, T-Lymphocyte %K Immunization, Secondary %K Immunologic Memory %K Influenza A virus %K Ligands %K Lymphocyte Activation %K Membrane Glycoproteins %K Mice %K Mice, Inbred C57BL %K Mice, Knockout %K Mice, Transgenic %K Receptors, Nerve Growth Factor %K Receptors, OX40 %K Receptors, Tumor Necrosis Factor %K Superantigens %K Tumor Necrosis Factor-alpha %K Tumor Necrosis Factors %X Mice deficient in OX40 or 4-1BB costimulatory pathways show defects in T cell recall responses, with predominant effects on CD4 vs CD8 T cells, respectively. However, OX40L can also stimulate CD8 T cells and 4-1BBL can influence CD4 T cells, raising the possibility of redundancy between the two TNFR family costimulators. To test this possibility, we generated mice deficient in both 4-1BBL and OX40L. In an adoptive transfer model, CD4 T cells expressed 4-1BB and OX40 sequentially in response to immunization, with little or no overlap in the timing of their expression. Under the same conditions, CD8 T cells expressed 4-1BB, but no detectable OX40. Thus, in vivo expression of 4-1BB and OX40 can be temporally and spatially segregated. In the absence of OX40L, there were decreased CD4 T cells late in the primary response and no detectable secondary expansion of adoptively transferred CD4 T cells under conditions in which primary expansion was unaffected. The 4-1BBL had a minor effect on the primary response of CD4 T cells in this model, but showed larger effects on the secondary response, although 4-1BBL(-/-) mice show less impairment in CD4 secondary responses than OX40L(-/-) mice. The 4-1BBL(-/-) and double knockout mice were similarly impaired in the CD8 T cell response, whereas OX40L(-/-) and double knockout mice were similarly impaired in the CD4 T cell response to both protein Ag and influenza virus. Thus, 4-1BB and OX40 act independently and nonredundantly to facilitate robust CD4 and CD8 recall responses. %B J Immunol %V 173 %P 5944-51 %8 2004 Nov 15 %G eng %N 10 %1 http://www.ncbi.nlm.nih.gov/pubmed/15528328?dopt=Abstract