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) 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 Google Scholar Articles by Tesciuba, A. G. Articles by Sperling, A. I. PubMed PubMed Citation Articles by Tesciuba, A. G. Articles by Sperling, A. I.

ICOS Costimulation Expands Th2 Immunity by Augmenting Migration of Lymphocytes to Draining Lymph Nodes¹

Amanda G. Tesciuba^2,*, Rebecca A. Shilling^2,3,*,, Monica D. Agarwal^*, Hozefa S. Bandukwala^*, Bryan S. Clay^*, Tamson V. Moore^*, Joel V. Weinstock, Andrew A. Welcher and Anne I. Sperling^*,

^* Committee on Immunology and Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637; Division of Gastroenterology-Hepatology, Department of Internal Medicine, Tufts New England Medical Center, Boston, MA 02111; and Department of Inflammation, Amgen Inc., Thousand Oaks, CA 91320

The T cell costimulatory molecule ICOS regulates Th2 effector function in allergic airway disease. Recently, several studies with ICOS^–/– mice have also demonstrated a role for ICOS in Th2 differentiation. To determine the effects of ICOS on the early immune response, we investigated augmenting ICOS costimulation in a Th2-mediated immune response to Schistosoma mansoni Ags. We found that augmenting ICOS costimulation with B7RP-1-Fc increased the accumulation of T and B cells in the draining lymph nodes postimmunization. Interestingly, the increased numbers were due in part to increased migration of undivided Ag-specific TCR transgenic T cells and surprisingly B cells, as well as non-TCR transgenic T cells. B7RP-1-Fc also increased the levels of the chemokines CCL21 and CXCL13 in the draining lymph node, suggesting ICOS costimulation contributes to migration by direct or indirect effects on dendritic cells, stromal cells and high endothelial venules. Further, the effects of B7RP-1-Fc were not dependent on immunization. Our data support a model in which ICOS costimulation augments the pool of lymphocytes in the draining lymph nodes, leading to an increase in the frequency of potentially reactive T and B cells.

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 National Institute of Health Grants R01 AI50180 (A.I.S.) and K08 AI059105 (R.A.S.) and a fellowship from the American Lung Association of Metropolitan Chicago (R.A.S.). M.D.A. was supported by a fellowship from the Howard Hughes Medical Institute undergraduate research program. The University of Chicago Flow Facility was supported in part by the University of Chicago Cancer Center National Institutes of Health Grant CA14559.

² A.G.T. and R.A.S. contributed equally and should be considered co-first authors.

³ Address correspondence and reprint requests to Dr. Rebecca A. Shilling, University of Chicago, MC6076, M658, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail address: rshillin{at}medicine.bsd.uchicago.edu

⁴ Abbreviations used in this paper: HFc, Human-Fc; DLN, draining lymph node; SEA, soluble egg antigen; LN, lymph node; Tg⁺, DO11.10 TCR transgenic T cell.