Mice Deficient in OX40 and CD30 Signals Lack Memory Antibody Responses because of Deficient CD4 T Cell Memory

• Published in: The Journal of immunology (1950) 2005-04, Vol.174 (7), p.3891-3896
• Main Authors: Gaspal, Fabrina M. C, Kim, Mi-Yeon, McConnell, Fiona M, Raykundalia, Chandra, Bekiaris, Vasilios, Lane, Peter J. L
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell Survival; Coculture Techniques; Germinal Center - immunology; Immunologic Memory; Ki-1 Antigen - genetics; Ki-1 Antigen - immunology; Membrane Glycoproteins - immunology; Mice; Mice, Knockout; Receptors, OX40; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - immunology; Signal Transduction - immunology; Tumor Necrosis Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.7.3891

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.