Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice.
C57BL/6 mice genetically deficient in interleukin 15 (IL-15(-/-) mice) were generated by gene targeting. IL-15(-/-) mice displayed marked reductions in numbers of thymic and peripheral natural killer (NK) T cells, memory phenotype CD8(+) T cells, and distinct subpopulations of intestinal intraepithelial lymphocytes (IELs). The reduction but not absence of these populations in IL-15(-/-) mice likely reflects an important role for IL-15 for expansion and/or survival of these cells. IL-15(-/-) mice lacked NK cells, as assessed by both immunophenotyping and functional criteria, indicating an obligate role for IL-15 in the development and functional maturation of NK cells. Specific defects associated with IL-15 deficiency were reversed by in vivo administration of exogenous IL-15. Despite their immunological defects, IL-15(-/-) mice remained healthy when maintained under specific pathogen-free conditions. However, IL-15(-/-) mice are likely to have compromised host defense responses to various pathogens, as they were unable to mount a protective response to challenge with vaccinia virus. These data reveal critical roles for IL-15 in the development of specific lymphoid lineages. Moreover, the ability to rescue lymphoid defects in IL-15(-/-) mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine.
Kennedy
M K
MK
Immunex Corporation, Seattle, Washington 98101, USA.
Glaccum
M
M
Brown
S N
SN
Butz
E A
EA
Viney
J L
JL
Embers
M
M
Matsuki
N
N
Charrier
K
K
Sedger
L
L
Willis
C R
CR
Brasel
K
K
Morrissey
P J
PJ
Stocking
K
K
Schuh
J C
JC
Joyce
S
S
Peschon
J J
JJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000033:anatomy & histology / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009929:Organ Size; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000033:anatomy & histology / Q000276:immunology; D013950:Thymus Gland / Q000033:anatomy & histology / Q000276:immunology; D014615:Vaccinia / Q000401:mortality
C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2