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The Journal of Immunology, 2008, 180, 747 -753
Copyright © 2008 by The American Association of Immunologists, Inc.
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Transgenic CD4 T Cells (DO11.10) Are Destroyed in MHC-Compatible Hosts by NK Cells and CD8 T Cells1

Darragh Duffy, Sheila M. Sparshott, Chun-ping Yang and Eric B. Bell2

Immunology Section, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom

During an immune response a small number of rare Ag-specific clones proliferate extensively and decline, leaving a residual population for long-term memory. TCR transgenic (tg) CD4 T cells have been used widely to study the primary and memory response in vivo. We show here that naive TCR tg CD4 T cells from the DO11.10 strain transferred into wild type (wt) BALB/c recipients and not stimulated declined rapidly at the same rate as those primed in vivo by Ag. In the same recipients wt CD4 T cells survived. There was no evidence of an inherent defect in the tg T cells, which survived well when returned to DO11.10 recipients. Surprisingly, wt CD4 T cells declined rapidly in the same DO11.10 hosts. By depleting wt recipients of NK cells or CD8+ cells, the speed of reduction was slowed by half; rapid destruction was prevented completely by combing the two treatments. In contrast, preimmunization accelerated the loss of tg T cells. The results suggested that tg CD4 T cells were actively rejected by both NK and CD8 T cell responses. We consider whether, despite extensive backcrossing, tg T cells may retain genetic material (minor histocompatibility Ags) flanking the construct that compromises their survival in wt recipients.

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 funds from the Dunhill Medical Trust and the University of Manchester.

2 Address correspondence and reprint requests to Dr. Eric B. Bell, Immunology Section, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, U.K. E-mail address: eric.bell{at}manchester.ac.uk

3 Abbreviations used in this paper: tg, transgenic; wt, wild type; ap, alum precipitation; ASGM1, anti-asialo GM1; BALB/cOlaHsd, BALB/c from Harlan-Olac; Jax-BALB, BALB/c strain from The Jackson Laboratory; LN, lymph node; NS, nonsynonymous; OVA-pep, OVA peptide 323–339; SNP, single nucleotide polymorphism; U.K.-BALB, BALB/c strain available in the United Kingdom.


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The JI 2008 180: 681-682. [Full Text]  





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