Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory

F Gaspal, MY Kim, FM McConnell… - The Journal of …, 2005 - journals.aai.org
F Gaspal, MY Kim, FM McConnell, C Raykundalia, V Bekiaris, PJL Lane
The Journal of Immunology, 2005journals.aai.org
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 …
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.
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