The molecular program induced in T cells undergoing homeostatic proliferation.
Naïve T cells proliferate independently of cognate antigen when introduced into lymphopenic hosts. Lymphopenia-induced proliferation depends on low-affinity MHC/self-peptide complexes and on IL-7. To elucidate the intracellular signals mediating this proliferation, we analyzed changes in gene expression in naive CD8+ T cells at different times after their transfer into a lymphopenic environment. The genes induced in response to lymphopenia were largely an attenuated subset of those turned up by full antigenic stimulation, including genes related to cell cycling, whereas excluding genes specifically associated with effector activity. After the initial phase of proliferation in an empty compartment, the naive T cells adopted a stable pattern of gene expression similar to that of antigen-experienced memory cells. Thus, T cells proliferating in lymphopenic hosts do not exhibit a unique gene-expression profile, instead relying on "traditional" signals for this antigen-independent proliferation; this process ultimately results in differentiation to "authentic" memory cells.
Goldrath
Ananda W
AW
Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Luckey
C John
CJ
Park
Richard
R
Benoist
Christophe
C
Mathis
Diane
D
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000276:immunology*; D015342:DNA Probes; D005260:Female; D020869:Gene Expression Profiling; D006706:Homeostasis; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015342:DNA Probes