Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells.
Both naive and memory T cells undergo antigen-independent proliferation after transfer into a T cell-depleted environment (acute homeostatic proliferation), whereas only memory T cells slowly divide in a full T cell compartment (basal proliferation). We show, first, that naive and memory CD8+ T cells have different cytokine requirements for acute homeostatic proliferation. Interleukin (IL)-7 receptor(R)alpha-mediated signals were obligatory for proliferation of naive T cells in lymphopenic hosts, whereas IL-15 did not influence their division. Memory T cells, on the other hand, could use either IL-7Ralpha- or IL-15-mediated signals for acute homeostatic proliferation: their proliferation was delayed when either IL-7Ralpha was blocked or IL-15 removed, but only when both signals were absent was proliferation ablated. Second, the cytokine requirements for basal and acute homeostatic proliferation of CD8+ memory T cells differ, as basal division of memory T cells was blocked completely in IL-15-deficient hosts. These data suggest a possible mechanism for the dearth of memory CD8+ T cells in IL-15- and IL-15Ralpha-deficient mice is their impaired basal proliferation. Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments.
Goldrath
Ananda W
AW
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. Ananda.Goldrath@joslin.harvard.edu
Sivakumar
Pallavur V
PV
Glaccum
Moira
M
Kennedy
Mary K
MK
Bevan
Michael J
MJ
Benoist
Christophe
C
Mathis
Diane
D
Butz
Eric A
EA
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000502:physiology*; D007156:Immunologic Memory / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
D017931:DNA Primers; D019409:Interleukin-15; D015851:Interleukin-7