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 Barthlott, T. Articles by Stockinger, B. Search for Related Content PubMed PubMed Citation Articles by Barthlott, T. Articles by Stockinger, B.

Normal Thymic Selection of TCR Transgenic CD4 T Cells, but Impaired Survival in the Periphery Despite the Presence of Selecting MHC Molecules

Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London, United Kingdom

In this paper, we investigate selection in the thymus and survival in the periphery of CD4 T cells, which carry a major histocompatibility class II-restricted transgenic TCR (A18 TCRtg) specific for a natural self Ag, the fifth component of complement (C5). A18 TCRtg thymocytes develop normal numbers of CD4 single-positive (SP) thymocytes, but do not show pronounced overselection as do some other TCR transgenic strains. CD4 SP cells are mature as judged by termination of CD8 synthesis, resistance to cortisone, and functional competence. The kinetics of positive selection, determined by BrdU labeling, are very fast. CD4 SP thymocytes are demonstrable within 2 days of labeling, and within 8 days after labeling a large proportion (20%) of lymph node T cells are recent thymic emigrants. The high number of recent thymic emigrants suggests rapid turnover of CD4 T cells in the periphery, which was confirmed by thymectomy and determination of CD4 T cell life spans. A18 TCRtg T cells have a t_1/2 of 6 wk, despite the presence of selecting MHC molecules. This explains the failure to accumulate high numbers of peripheral T cells and suggests that the MHC-bound ligand(s) responsible for initiating survival signals is limiting for the selection and maintenance of A18 transgenic CD4 T cells.

This article has been cited by other articles:

				L. Kuffova, M. Netukova, L. Duncan, A. Porter, B. Stockinger, and J. V. Forrester Cross Presentation of Antigen on MHC Class II via the Draining Lymph Node after Corneal Transplantation in Mice J. Immunol., February 1, 2008; 180(3): 1353 - 1361. [Abstract] [Full Text] [PDF]

				G. Kassiotis, R. Zamoyska, and B. Stockinger Involvement of Avidity for Major Histocompatibility Complex in Homeostasis of Naive and Memory T Cells J. Exp. Med., April 21, 2003; 197(8): 1007 - 1016. [Abstract] [Full Text] [PDF]

				C. Viret and C. A. Janeway Jr. Self-Specific MHC Class II-Restricted CD4-CD8- T Cells That Escape Deletion and Lack Regulatory Activity J. Immunol., January 1, 2003; 170(1): 201 - 209. [Abstract] [Full Text] [PDF]

				C. Viret, X. He, and C. A. Janeway Jr. On the Self-Referential Nature of Naive MHC Class II-Restricted T Cells J. Immunol., December 1, 2000; 165(11): 6183 - 6192. [Abstract] [Full Text] [PDF]

				J. B. Reome, D. S. Johnston, B. K. Helmich, T. M. Morgan, N. Dutton-Swain, and R. W. Dutton The Effects of Prolonged Administration of 5-Bromodeoxyuridine on Cells of the Immune System J. Immunol., October 15, 2000; 165(8): 4226 - 4230. [Abstract] [Full Text] [PDF]

				C. Ferreira, T. Barthlott, S. Garcia, R. Zamoyska, and B. Stockinger Differential Survival of Naive CD4 and CD8 T Cells J. Immunol., October 1, 2000; 165(7): 3689 - 3694. [Abstract] [Full Text] [PDF]

				K. Murali-Krishna, L. L. Lau, S. Sambhara, F. Lemonnier, J. Altman, and R. Ahmed Persistence of Memory CD8 T Cells in MHC Class I-Deficient Mice Science, November 12, 1999; 286(5443): 1377 - 1381. [Abstract] [Full Text]