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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ramanathan, S. Articles by Ilangumaran, S. Search for Related Content PubMed PubMed Citation Articles by Ramanathan, S. Articles by Ilangumaran, S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH

Suppressor of Cytokine Signaling 1 Stringently Regulates Distinct Functions of IL-7 and IL-15 In Vivo during T Lymphocyte Development and Homeostasis¹

Sheela Ramanathan^*, Julien Gagnon^*, Chantal Leblanc^*, Robert Rottapel and Subburaj Ilangumaran^2,*

^* Immunology Division, Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Canada; and Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Canada

SOCS1^–/– mice accumulate within the thymus and periphery CD8⁺ lymphocytes that express memory cell markers and display heightened in vitro responses to common -chain cytokines. To investigate whether dysregulated homeostasis of T lymphocytes and acquisition of memory phenotype by CD8⁺ cells in SOCS1^–/– mice were mediated by IL-7 and/or IL-15 in vivo, we have generated SOCS1^–/–IL-7^–/–, SOCS1^–/–IL-15^–/– and SOCS1^–/–IL-7^–/–IL-15^–/– mice. We observed that in mice lacking SOCS1, either IL-7 or IL-15 skewed thymocyte development toward CD8 lineage, whereas IL-15 is the principal mediator of dysregulated homeostasis in the periphery. Homeostatic proliferation of SOCS1^–/– CD8⁺ lymphocytes in Rag1^–/–, Rag1^–/–IL-7^–/–, Rag1^–/–IL-15^–/–, and Rag1^–/–IL-7^–/–IL-15^–/– mice showed that SOCS1 deficiency did not overcome the requirement for IL-7 and IL-15 to sustain homeostatic expansion. Differential expression of memory phenotype markers CD44, CD122, and Ly6C by SOCS1^–/–IL-15^–/– CD8⁺ lymphocytes suggest that multiple signals contributed to the memory cell differentiation program. To address whether increased IL-15 responsiveness of SOCS1^–/– CD8⁺ lymphocytes required prior TCR sensitization, we generated SOCS1^–/– H-Y TCR transgenic (Tg) mice. Using female SOCS1^–/– H-Y TCR^tg mice in Rag1^+/+ and Rag1^–/– backgrounds, we show that acquisition of the memory phenotype by SOCS1-deficient CD8⁺ lymphocytes did not require prior antigenic stimulation, but required the presence of activated T cells. SOCS1 deficiency accelerated the maturation of CD8 single-positive thymocytes expressing Tg TCR, but did not compromise negative selection in HY-TCR^tg males. Our findings illustrate distinct functions for IL-7 and IL-15 in T lymphocyte development and homeostasis, and stringent regulation of these processes by SOCS1.

This article has been cited by other articles:

				S. D. Liu, C. C. Whiting, T. Tomassian, M. Pang, S. J. Bissel, L. G. Baum, V. V. Mossine, F. Poirier, M. E. Huflejt, and M. C. Miceli Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions in thymocytes Blood, July 1, 2008; 112(1): 120 - 130. [Abstract] [Full Text] [PDF]