HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901514v1 183/8/5079    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Withers, D. R. Articles by Lane, P. J. L. PubMed PubMed Citation Articles by Withers, D. R. Articles by Lane, P. J. L.

The Survival of Memory CD4⁺ T Cells within the Gut Lamina Propria Requires OX40 and CD30 Signals¹

David R. Withers,^23* Elin Jaensson,² Fabrina Gaspal,^* Fiona M. McConnell,^* Bertus Eksteen,^* Graham Anderson,^* William W. Agace, and Peter J. L. Lane^*

^*Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Birmingham, United Kingdom; and Immunology Section, Lund University, BMCD14, Lund, Sweden

Although CD4⁺ memory T cells reside within secondary lymphoid tissue, the major reservoir of these cells is in the lamina propria of the intestine. In this study, we demonstrate that, in the absence of signals through both OX40 and CD30, CD4⁺ T cells are comprehensively depleted from the lamina propria. Deficiency in either CD30 or OX40 alone reduced CD4⁺ T cell numbers, however, in mice deficient in both OX40 and CD30, CD4⁺ T cell loss was greatly exacerbated. This loss of CD4⁺ T cells was not due to a homing defect because CD30 x OX40-deficient OTII cells were not impaired in their ability to express CCR9 and ₄β₇ or traffic to the small intestine. There was also no difference in the priming of wild-type (WT) and CD30 x OX40-deficient OTII cells in the mesenteric lymph node after oral immunization. However, following oral immunization, CD30 x OX40-deficient OTII cells trafficked to the lamina propria but failed to persist compared with WT OTII cells. This was not due to reduced levels of Bcl-2 or Bcl-XL, because expression of these was comparable between WT and double knockout OTII cells. Collectively, these data demonstrate that signals through CD30 and OX40 are required for the survival of CD4⁺ T cells within the small intestine lamina propria.

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 Trust Programme Grant (to P.J.L.L. and G.A.) with input from grants from the Swedish Medical Research Council and the Swedish foundation for Strategic Research INGVAR II program (to W.W.A.).

² D.R.W. and E.J. contributed equally to this study.

³ Address correspondence and reprint requests to David Withers, Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, Birmingham Medical School, Birmingham, U.K. E-mail address: d.withers{at}bham.ac.uk

⁴ Abbreviations used in this paper: LP, lamina propria; TNFR, TNF receptor; KO, knockout; dKO, double KO; WT, wild type; PP, Peyer’s patch; mLN, mesenteric LN; DC, dendritic cell; LTi, lymphoid tissue inducer cell; DAPI, 4',6-diamidino-2-phenylindole dihydrochloride.