Distinct cell types control lymphoid subset development by means of IL-15 and IL-15 receptor alpha expression.
IL-15 and the IL-15 receptor (IL-15R)alpha chain are essential for normal development of naive CD8 T cells, intestinal intraepithelial lymphocytes (IEL), and natural killer (NK)/NK/T cells. However, whether IL-15R alpha expression by these subsets is necessary for their production and which cell type needs to produce IL-15 to drive development are unknown. We analyzed the requirements for IL-15 and IL-15R alpha expression by bone marrow-derived or parenchymal cells for mediating lymphocyte subset development. Naive CD8 T cell development required IL-15R alpha expression by both bone marrow-derived and parenchymal cells, whereas memory-phenotype CD8 T cells required IL-15R alpha expression only by hematopoietic cells. In contrast and surprisingly, the development of IEL subsets, particularly CD8 alpha alpha Thy1(-)V gamma 5(+) T cell antigen receptor gamma delta and the CD8 alpha alpha Thy1(-) T cell antigen receptor alpha beta IEL populations, depended completely on parenchymal cell expression of IL-15R alpha and IL-15 but not IL-15R beta. In the case of NK and NK/T cell generation and maturation, expression of IL-15 and IL-15R alpha by both parenchymal and hematopoietic cells was important, although the latter played the greatest role. These results demonstrated dichotomous mechanisms by which IL-15 regulated lymphoid development, interacting with distinct cell types depending on the developmental pathway.
Schluns
Kimberly S
KS
Department of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA.
Nowak
Elizabeth C
EC
Cabrera-Hernandez
Arturo
A
Puddington
Lynn
L
Lefrançois
Leo
L
Aguila
Hector L
HL
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000096:biosynthesis / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D018183:Transplantation Chimera
C508025:Il15ra protein, mouse; D019409:Interleukin-15; D016693:Receptors, Antigen, T-Cell, alpha-beta; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2