Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation.
In a depleted lymphoid compartment, naive T cells begin a slow proliferation that is independent of cognate antigen yet requires recognition of major histocompatibility complex-bound self-peptides. We have followed the phenotypic and functional changes that occur when naive CD8(+) T cells undergo this type of expansion in a lymphopenic environment. Naive T cells undergoing homeostasis-driven proliferation convert to a phenotypic and functional state similar to that of memory T cells, yet distinct from antigen-activated effector T cells. Naive T cells dividing in a lymphopenic host upregulate CD44, CD122 (interleukin 2 receptor beta) and Ly6C expression, acquire the ability to rapidly secrete interferon gamma, and become cytotoxic effectors when stimulated with cognate antigen. The conversion of naive T cells to cells masquerading as memory cells in response to a homeostatic signal does not represent an irreversible differentiation. Once the cellularity of the lymphoid compartment is restored and the T cells cease their division, they regain the functional and phenotypic characteristics of naive T cells. Thus, homeostasis-driven proliferation provides a thymus-independent mechanism for restoration of the naive compartment after a loss of T cells.
Goldrath
A W
AW
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Bogatzki
L Y
LY
Bevan
M J
MJ
D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D016654:Genes, RAG-1 / Q000235:genetics / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008231:Lymphopenia; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism
D000950:Antigens, Ly; D018960:Hyaluronan Receptors; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma