An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2.
In conditions of T lymphopenia, interleukin (IL) 7 levels rise and, via T cell receptor for antigen-self-major histocompatibility complex (MHC) interaction, induce residual naive T cells to proliferate. This pattern of lymphopenia-induced "homeostatic" proliferation is typically quite slow and causes a gradual increase in total T cell numbers and differentiation into cells with features of memory cells. In contrast, we describe a novel form of homeostatic proliferation that occurs when naive T cells encounter raised levels of IL-2 and IL-15 in vivo. In this situation, CD8(+) T cells undergo massive expansion and rapid differentiation into effector cells, thus closely resembling the T cell response to foreign antigens. However, the responses induced by IL-2/IL-15 are not seen in MHC-deficient hosts, implying that the responses are driven by self-ligands. Hence, homeostatic proliferation of naive T cells can be either slow or fast, with the quality of the response to self being dictated by the particular cytokine (IL-7 vs. IL-2/IL-15) concerned. The relevance of the data to the gradual transition of naive T cells into memory-phenotype (MP) cells with age is discussed.
Cho
Jae-Ho
JH
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Boyman
Onur
O
Kim
Hee-Ok
HO
Hahm
Bumsuk
B
Rubinstein
Mark P
MP
Ramsey
Chris
C
Kim
David M
DM
Surh
Charles D
CD
Sprent
Jonathan
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis; D008024:Ligands; D008285:Major Histocompatibility Complex; D051379:Mice; D008954:Models, Biological; D010641:Phenotype
D019409:Interleukin-15; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D008024:Ligands