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) Data Supplement All Versions of this Article: jimmunol.0804339v1 183/7/4493    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 Shi, M. Articles by Berg, L. J. PubMed PubMed Citation Articles by Shi, M. Articles by Berg, L. J.

Cell Cycle Progression following Naive T Cell Activation Is Independent of Jak3/Common -Chain Cytokine Signals¹

Min Shi^*, Tsung H. Lin, Kenneth C. Appell and Leslie J. Berg^2,*

^* Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; and Pharmacopeia Inc., Princeton, NJ 08540

T cell proliferation following activation is an essential aspect of the adaptive immune response. Multiple factors, such as TCR signaling, costimulation, and signals from cytokines, each contribute to determine the magnitude of T cell expansion. In this report, we examine in detail the role of Jak3/common -chain-dependent cytokines in promoting cell cycle progression and proliferation of naive T cells. Using naive CD4⁺ T cells from Jak3-deficient mice and wild-type CD4⁺ T cells treated with a small molecule inhibitor of Jak3, we find that these cytokine signals are not required for proliferation; instead, they are important for the survival of activated T cells. In addition, we show that the percentage of cells entering the cell cycle and the percentage of cells in each round of cell division are comparable between Jak3-deficent and wild-type T cells. Furthermore, cell cycle progression and the regulated expression of key cell cycle proteins are independent of Jak3/common -chain cytokine signals. These findings hold true over a wide range of TCR signal strengths. However, when CD28 costimulatory signals, but not TCR signals, are limiting, Jak3-dependent cytokine signals become necessary for the proliferation of naive T cells. Because CD28 signaling has been found to be dispensable for autoreactive T cell responses, these data suggest the potential for interfering with autoimmune T cell responses by inhibition of Jak3 signaling.

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 Institutes of Health Grants AI46564 and AI37584. Core resources supported by the Diabetes Endocrinology Research Center Grant DK32520 were also used.

² Address correspondence and reprint requests to Dr. Leslie J. Berg, Department of Pathology, S3-143B, University of Massachusetts Medical School. 55 Lake Avenue North. Worcester, MA 01655. E-mail address: leslie.berg{at}umassmed.edu

³ Abbreviations used in this paper: cdk, cyclin-dependent kinase; CDKI, cyclin-dependent kinase inhibitor; Rb, retinoblastoma; _c, common -chain; SP, single positive; 7-AAD, 7-aminoactinomycin D; BH, Bcl-2 homology.

⁴ The online version of this article contains supplemental material.