The Journal of Experimental Medicine
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Published online 29 September 2003 doi:10.1084/jem.20030963
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© Rockefeller University Press, 0022-1007/2003/10/1089 $5.00
The Journal of Experimental Medicine, Volume 198, Number 7, 1089-1102

Are Major Histocompatibility Complex Molecules Involved in the Survival of Naive CD4+ T Cells?

Isabelle Grandjean1, Livine Duban1, Elizabeth A. Bonney2,3, Erwan Corcuff4, James P. Di Santo4, Polly Matzinger2 and Olivier Lantz1

1 Laboratoire d'Immunologie and INSERM U520, Institut Curie, 75005 Paris, France
2 The Ghost Lab, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892
3 Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, VT 05405
4 Unité des Cytokines et Développement Lymphoïde, INSERM, EMI 0101, Institut Pasteur, 75015 Paris, France

Address correspondence to Olivier Lantz, Laboratoire d'Immunologie, Institut Curie, 26 rue d'Ulm, 75005 Paris, France. Phone: 33-1-44-32-42-18; Fax: 33-1-44-32-44-44; email: olivier.lantz{at}curie.net

The exact role of major histocompatibility complex (MHC) molecules in the peripheral survival of naive T cells is controversial, as some studies have suggested that they are critically required whereas others have suggested that they are not. Here we controlled for some of the features that differed among the earlier studies, and analyzed both the survival and expansion of naive CD4+ T cells transferred into MHC syngeneic, allogeneic, or MHC negative environments. We found that naive T cells transferred into MHC negative or allogeneic environments often fail to survive because of rejection and/or competition by natural killer (NK) cells, rather than failure to recognize a particular MHC allele. In the absence of NK cells, naive CD4+ T cells survived equally well regardless of the MHC type of the host. There was, however, an MHC requirement for extensive space-induced "homeostatic" expansion. Although the first few divisions occurred in the absence of MHC molecules, the cells did not continue to divide or transit to a CD44hi phenotype. Surprisingly, this MHC requirement could be satisfied by alleles other than the restricting haplotype. Therefore, space-induced expansion and survival are two different phenomena displaying different MHC requirements. Memory CD4+ T cells, whose survival and expansion showed no requirements for MHC molecules at all, dampened the space-induced expansion of naive cells, showing that the two populations are not independent in their requirements for peripheral niches.

Key Words: T cell • naive • MHC • homeostasis


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