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. 2001 Jul 17;98(15):8732-7.
doi: 10.1073/pnas.161126098. Epub 2001 Jul 10.

IL-7 is critical for homeostatic proliferation and survival of naive T cells

J T Tan  1 , E Dudl, E LeRoy, R Murray, J Sprent, K I Weinberg, C D Surh
Affiliations

IL-7 is critical for homeostatic proliferation and survival of naive T cells

J T Tan et al. Proc Natl Acad Sci U S A. .

Abstract

In T cell-deficient conditions, naive T cells undergo spontaneous "homeostatic" proliferation in response to contact with self-MHC/peptide ligands. With the aid of an in vitro system, we show here that homeostatic proliferation is also cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic proliferation of naive T cells in vitro. Of these cytokines, only IL-7 was found to be critical; thus, naive T cells underwent homeostatic proliferation in IL-4(-) and IL-15(-) hosts but proliferated minimally in IL-7(-) hosts. In addition to homeostatic proliferation, the prolonged survival of naive T cells requires IL-7. Thus, naïve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7(-) hosts. These findings indicate that naive T cells depend on IL-7 for survival and homeostatic proliferation.

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Figures

Figure 1
Figure 1
Homeostatic proliferation of RAG-1− OT-I TCR transgenic T cells in vitro. Small doses (2–5 × 106 cell/mouse) of CFSE-labeled LN cells from OT-I mice in a RAG-1-deficient background were injected into various irradiated (600 cGy,1 day before) or unirradiated hosts. For in vitro analysis, LNs from host mice were removed 15 h after injection of donor OT-I cells. Whole LNs and spleen fragments were cultured for 7 days as described in Materials and Methods. For in vivo analysis, LNs from host mice were harvested 8 days after donor cell injection. Shown are CFSE profiles of gated donor OT-I cells (CD8+ Vα2+) or CD8 and Vα2 staining on all cells. Similar results were obtained with spleens.
Figure 2
Figure 2
Expression of receptors for IL-2, IL-7, and IL-15 and the common cytokine γ chain (γc) on LN T cells from TCR transgenic and normal B6 mice. LN cells from B6, RAG-1− OT-I, and 2C mice were triple-stained for expression of the indicated cytokine receptors and CD4 and CD8. Shown are gated CD4+ or CD8+ cells that were stained for the indicated receptors (filled) or background staining with rat IgG (unfilled).
Figure 3
Figure 3
IL-4, IL-7, and IL-15 promote proliferation of TCR transgenic and normal CD8+ cells in LO cultures. (A) LNs from irradiated (600 cGy) B6 or β2m−Kb−Db− mice previously injected with CFSE-labeled RAG-1− OT-I cells were cultured in vitro in media only or in media supplemented with recombinant cytokines (10 ng/ml) for 7 days. Shown are CFSE profiles of gated donor OT-I cells. (B) LNs from irradiated (600 cGy) B6 mice previously injected with CFSE-labeled normal polyclonal LN cells from Thy-1-congenic B6.PL LN cells were incubated with or without the indicated cytokines (10 ng/ml) for 7 days. Shown are gated donor CD4+ (Thy-1.1+ CD8−) and CD8+ (Thy-1.1+ CD8+) cells.
Figure 4
Figure 4
Blocking signaling through the γc prevents survival and homeostatic proliferation of naïve T cells. LNs from irradiated B6 mice previously injected with CFSE-labeled Rag-1− OT-I LN cells were cultured in vitro in media supplemented with normal rat IgG (50 μg/ml), mAb to IL-2Rβ (clone TMβ-1, 50 μg/ml), or a mixture of mAbs to γc (clones 4G3, 3E12, and TUGm2 at 20 μg/ml each) for 7 days. Shown are Vα2 and CD8 staining on all viable cells, CFSE levels on gated donor OT-I cells, and the total numbers of cells recovered from the three cultures.
Figure 5
Figure 5
Homeostatic proliferation of naïve T cells in vivo crucially depends on IL-7. Groups of irradiated (600 cGy) normal B6 mice and B6 mice deficient in IL-4, IL-7, or IL-15 were injected with 2C, RAG-1− OT-I, or B6.PL LN cells. LNs from host mice were harvested 7 days later and stained for donor markers. Shown are CFSE levels of gated donor T cells.
Figure 6
Figure 6
Restoration of homeostatic proliferation of OT-I cells in IL-7− mice by addition of exogenous IL-7 but not by up-regulation of bcl-2. (Left) Groups of irradiated B6.IL-7− mice were injected with RAG-1− OT-I LN cells. For in vivo analysis, mice were either injected with PBS or 500 ng of recombinant IL-7 every 12 h for 7 days. For in vitro analysis, spleen fragments from the hosts were treated with media only or media containing 40 ng/ml IL-7 for 7 days. Irradiated B6 hosts injected with OT-I cells and analyzed either in vivo or in vitro conditions served as controls. Shown are gated donor cells. (Right) A group of irradiated B6 mice was injected with a mixture of wild-type B6.PL and B6.Ly5.1 bcl-2 transgenic cells. Mice were analyzed 7 days later by staining LN cells for Thy-1.1, Ly5.1, and CD8; shown are gated CD8+ cells.
Figure 7
Figure 7
Survival of naïve T cells requires IL-7. CFSE labeled purified LN CD4 and CD8 T cells (15 × 106 cells/mouse) from B6. Ly5.1 mice were labeled with CFSE and transferred into unirradiated B6 (unfilled) or IL-7− (filled) hosts. One, 17, and 30 days after transfer, spleen cells were harvested, and donor CFSEhi CD8+ T cells (squares) were detected by staining for Ly5.1 and CD8. Donor CD4+ T cells (circles) are Ly5.1+, CFSEhi, and CD8− T cells. Total numbers of donor CFSEhi cells recovered from host LN and spleens (2–3 hosts analyzed individually per time point) are shown.
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References

    1. Freitas A A, Rocha B B. Immunol Today. 1993;14:25–29. - PubMed
    1. Bell E B, Sparshott S M. Semin Immunol. 1997;9:347–353. - PubMed
    1. Goldrath A W, Bevan M J. Nature (London) 1999;402:255–262. - PubMed
    1. Surh C D, Sprent J. J Exp Med. 2000;192:F9–F14. - PMC - PubMed
    1. Tanchot C, Rosado M M, Agenes F, Freitas A A, Rocha B. Semin Immunol. 1997;9:331–337. - PubMed

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