IL-15 availability conditions homeostasis of peripheral natural killer T cells.
Steady-state numbers of peripheral lymphocyte are tightly controlled. For conventional T cells, signals delivered through the interaction of the T cell receptor (TCR) with antigen-loaded MHC molecules are required for the peripheral survival of naive T cells and for their homeostatic expansion in lymphopenic hosts. Cytokines, including IL-7, are also essential for survival of peripheral naive T cells. CD1d-restricted, V alpha 14(+) natural killer (NK)-T cells are a specialized autoreactive T subset with immunoregulatory activity. The relative roles of TCR engagement and cytokine signaling in the peripheral homeostasis of V alpha 14(+) NK-T cells were investigated. After adoptive transfer, the survival and expansion of peripheral V alpha 14(+) NK-T cells was independent of CD1d expression in the host. In contrast, IL-15 (but not IL-7) was required for maintenance of peripheral CD1d-reactive V alpha 14(+) T cells. Comparison of V alpha 14(+) T cell transfers into NK-proficient vs. deficient hosts suggests that NK-T cells and NK cells compete for peripheral resources. Our results indicate that IL-15 maintains the homeostasis of peripheral V alpha 14(+) NK-T cells. In contrast, TCR "tickling" of NK-T cells, if it occurs under steady-state conditions, does not by itself provide a sufficient signal for their peripheral survival.
Ranson
Thomas
T
Unité des Cytokines et Développement Lymphoide Institut National de la Santé et de la Recherche Médicale Equipe 101, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.
Vosshenrich
Christian A J
CA
Corcuff
Erwan
E
Richard
Odile
O
Laloux
Veronique
V
Lehuen
Agnès
A
Di Santo
James P
JP
D019264:Adoptive Transfer; D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002455:Cell Division; D002470:Cell Survival; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors
D018949:Antigens, CD1; D055610:Antigens, CD1d; D019409:Interleukin-15; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001973:Bromodeoxyuridine