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CD30 Is Required for CCL21 Expression and CD4 T Cell Recruitment in the Absence of Lymphotoxin Signals¹

Vasileios Bekiaris^2,*, Fabrina Gaspal, Mi-Yeon Kim, David R. Withers, Fiona M. McConnell, Graham Anderson and Peter J. L. Lane^3,

^* La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Medical Research Council Centre for Immune Regulation, Birmingham Medical School, Birmingham, United Kingdom; and Department of Bioinformatics and Life Sciences, Soongsil University, Seoul, Korea

Lymphoid tissue inducer cells express a diverse array of tumor necrosis family ligands, including those that bind CD30 and the lymphotoxin β receptor. Both of these signaling pathways have been linked with B/T segregation in the spleen. In this study, we have dissected a lymphotoxin-independent CD30-dependent signal for the induction of expression of the T zone chemokine, CCL21. Reduced expression of CCL21 due to CD30 deficiency was functionally significant: mice deficient in both lymphotoxin and CD30 (dKO) signals had significantly smaller accumulations of lymphocytes in their splenic white pulp areas, with no evidence of focal aggregation of T cells. Furthermore, recruitment of wild-type CD4 T cells was poor in dKO mice compared with both wild-type or lymphotoxin-deficient mice. Phylogeny suggests that CD30 signals predated those through the lymphotoxin β receptor. We suggest that CD30 signals from lymphoid tissue inducer cells were a primitive mechanism to recruit and prime CD4 T cells. This would have been a stepping stone in the evolution of the highly organized lymphotoxin dependent B and T white pulp areas within which CD4-dependent memory Ab responses now develop.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Wellcome Programme Grant (to P.J.L.L. and G.A.).

² Current address: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037.

³ Address correspondence and reprint requests to Dr. P. J. L. Lane, Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham, U.K. E-mail address p.j.l.lane{at}bham.ac.uk

⁴ Abbreviations used in this paper: DC, dendritic cell; LTβR, lymphotoxin β receptor; LTi, lymphoid tissue inducer cell; WT, wild type.