Naive T Cells Transiently Acquire a Memory-like Phenotype during Homeostasis-Driven Proliferation

By Ananda W. Goldrath, L. Bogatzki, M. Bevan. Journal of Experimental Medicine, 2000

762 citations recorded by the source corpus.

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 β) and Ly6C expression, acquire the ability to rapidly secrete interferon γ, 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/0053a8d33331b864d8fa64d52d3b1e51eb524fed

How researchers see this paper

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In Immunology

1. Alexander Y. Rudensky
2. Joseph C. Sun
3. M. Bevan
4. L. Lanier
5. V. Badovinac
6. J. Harty
7. D. Mathis
8. C. Benoist

In Oncology

1. Alexander Y. Rudensky
2. L. Lanier
3. M. Bevan

Citations in the corpus

• Homeostasis and anergy of CD4+CD25+ suppressor T cells in vivo (2002, background): “This enhanced activity was reminiscent of the finding that CD8 + T cell effector functions are also augmented by homeostatic proliferatio”
• Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T Cells (2002, methodology): “2 ) hosts followed by intravenous infection 1 d later with 5 10 6 PFU of Vaccinia virus carrying OVA cDNA (27).”
• NK cell development, homeostasis and function: parallels with CD8+ T cells (2011, background): “Like CD8 + T cells, NK cells become phenotypically activated during homeostatic proliferation, and this involves the upregulation of markers such as CD11a, CD44, CD122 and LY6”
• Differentiation and persistence of memory CD8+ T cells depend on T cell factor 1 (2010, background): “Whereas CD44hi CD8+ T cells produced IFN-g after brief TCR stimulation (Cho et al., 2000; Goldrath et al., 2000), the TCR-stimulated IFN-g production was negligible in both WT and Tcf7 / CD44lo CD8+ T cells (Figure S2D).”