@article {542576,
	title = {4-1BB and OX40 act independently to facilitate robust CD8 and CD4 recall responses.},
	journal = {J Immunol},
	volume = {173},
	number = {10},
	year = {2004},
	month = {2004 Nov 15},
	pages = {5944-51},
	abstract = {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.},
	keywords = {4-1BB Ligand, Adoptive Transfer, Animals, Antigens, CD, Antigens, CD137, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Enterotoxins, Epitopes, T-Lymphocyte, Immunization, Secondary, Immunologic Memory, Influenza A virus, Ligands, Lymphocyte Activation, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, Nerve Growth Factor, Receptors, OX40, Receptors, Tumor Necrosis Factor, Superantigens, Tumor Necrosis Factor-alpha, Tumor Necrosis Factors},
	issn = {0022-1767},
	author = {Dawicki, Wojciech and Bertram, Edward M and Sharpe, Arlene H and Watts, Tania H}
}
