title: Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory.
abstract: Recently, we reported that a CD4(+)CD3(-)CD11c(-) accessory cell provided OX40-dependent survival signals to follicular T cells. These accessory cells express both OX40 ligand and CD30 ligand, and the receptors, OX40 and CD30, are both expressed on Th2-primed CD4 T cells. OX40 and CD30 signals share common signaling pathways, suggesting that CD30 signals might substantially compensate in OX40-deficient mice. In this report we have dissected the signaling roles of CD30 alone and in combination with OX40. CD30-deficient mice showed an impaired capacity to sustain follicular germinal center responses, and recall memory Ab responses were substantially reduced. Deficiencies in OX40 and CD30 signals were additive; secondary Ab responses were ablated in double-deficient mice. Although the initial proliferation of OX40/CD30 double-knockout OTII transgenic T cells was comparable to that of their normal counterparts, they failed to survive in vivo, and this was associated with reduced T cell numbers associated with CD4(+)CD3(-) cells in B follicles. Finally, we show that OX40/CD30 double-knockout OTII transgenic T cells fail to survive compared with normal T cells when cocultured with CD4(+)CD3(-) cells in vitro.
authors.affiliation: Medical Research Council Center for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham, United Kingdom.
authors.forename: Fabrina M C
authors.initials: FM
authors.lastname: Gaspal
authors.forename: Mi-Yeon
authors.initials: MY
authors.lastname: Kim
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McConnell
authors.forename: Chandra
authors.initials: C
authors.lastname: Raykundalia
authors.forename: Vasilios
authors.initials: V
authors.lastname: Bekiaris
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival; D018920:Coculture Techniques; D018858:Germinal Center / Q000276:immunology; D007156:Immunologic Memory; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D048069:Tumor Necrosis Factors
chemical_list: D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors