IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2003 Dec 17

PMID 14676295

Citations 133

Authors

Jichu Li

Gail Huston

Susan L Swain

Affiliations

Soon will be listed here.

Abstract

After transfer to adoptive hosts, in vitro-generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown. We find that low doses of interleukin (IL) 7 enhance survival of effectors in vitro without driving their division. When in vitro-generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype. CD4 effectors generated from wild-type versus IL-7 receptor-/- mice were transferred to adoptive hosts, including intact mice and those deficient in IL-7. In each case, the response to IL-7 was critical for good recovery of donor cells after 5-7 d. Recovery was also IL-7-dependent in Class II hosts where division was minimal. Blocking antibodies to IL-7 dramatically decreased short-term recovery of transferred effectors in vivo without affecting their division. These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.

Citing Articles

Activation of Cell-Intrinsic Signaling in CAR-T Cells via a Chimeric IL7R Domain.

Vorri S, Holl N, Leeming M, Apostolova P, Marple A, Ravich J Cancer Res Commun. 2024; 4(9):2359-2373.

PMID: 39186002 PMC: 11382189. DOI: 10.1158/2767-9764.CRC-24-0286.

T Cell Subsets and Immune Homeostasis.

Wu C, Jiang M, Pang T, Zhang C Methods Mol Biol. 2024; 2782:39-63.

PMID: 38622391 DOI: 10.1007/978-1-0716-3754-8_3.

Novel Synonymous Variant in IL7R Causes Preferential Expression of the Soluble Isoform.

Mackeh R, El Bsat Y, Elmi A, Bibawi H, Karim M, Hassan A J Clin Immunol. 2024; 44(4):96.

PMID: 38587703 PMC: 11001715. DOI: 10.1007/s10875-024-01688-8.

A novel memory-like Tfh cell subset is precursor to effector Tfh cells in recall immune responses.

Feng H, Zhao Z, Zhao X, Bai X, Fu W, Zheng L J Exp Med. 2023; 221(1).

PMID: 38047912 PMC: 10695277. DOI: 10.1084/jem.20221927.

CD4 Effector TCR Avidity for Peptide on APC Determines the Level of Memory Generated.

Jones M, Castonguay C, Nanaware P, Weaver G, Stadinski B, Kugler-Umana O J Immunol. 2023; 210(12):1950-1961.

PMID: 37093656 PMC: 10247507. DOI: 10.4049/jimmunol.2200337.

References

Swain S, Hu H, Huston G . Class II-independent generation of CD4 memory T cells from effectors. Science. 1999; 286(5443):1381-3. DOI: 10.1126/science.286.5443.1381. View

Hildeman D, Mitchell T, Teague T, Henson P, Day B, Kappler J . Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity. 1999; 10(6):735-44. DOI: 10.1016/s1074-7613(00)80072-2. View

Dalton D, Haynes L, Chu C, Swain S, Wittmer S . Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells. J Exp Med. 2000; 192(1):117-22. PMC: 1887703. DOI: 10.1084/jem.192.1.117. View

Lepak N, Yen M, Swain S . Two distinct stages in the transition from naive CD4 T cells to effectors, early antigen-dependent and late cytokine-driven expansion and differentiation. J Immunol. 2000; 165(9):5017-26. DOI: 10.4049/jimmunol.165.9.5017. View

Schluns K, Kieper W, Jameson S, Lefrancois L . Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo. Nat Immunol. 2001; 1(5):426-32. DOI: 10.1038/80868. View

Lantz O, Grandjean I, Matzinger P, Di Santo J . Gamma chain required for naïve CD4+ T cell survival but not for antigen proliferation. Nat Immunol. 2001; 1(1):54-8. DOI: 10.1038/76917. View

Vivien L, Benoist C, Mathis D . T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo. Int Immunol. 2001; 13(6):763-8. DOI: 10.1093/intimm/13.6.763. View

Tan J, Dudl E, Leroy E, Murray R, Sprent J, Weinberg K . IL-7 is critical for homeostatic proliferation and survival of naive T cells. Proc Natl Acad Sci U S A. 2001; 98(15):8732-7. PMC: 37504. DOI: 10.1073/pnas.161126098. View

Hu H, Huston G, Duso D, Lepak N, Roman E, Swain S . CD4(+) T cell effectors can become memory cells with high efficiency and without further division. Nat Immunol. 2001; 2(8):705-10. DOI: 10.1038/90643. View

10.

Chen W, Jin W, Tian H, Sicurello P, Frank M, Orenstein J . Requirement for transforming growth factor beta1 in controlling T cell apoptosis. J Exp Med. 2001; 194(4):439-53. PMC: 2193497. DOI: 10.1084/jem.194.4.439. View

11.

Rathmell J, Farkash E, Gao W, Thompson C . IL-7 enhances the survival and maintains the size of naive T cells. J Immunol. 2001; 167(12):6869-76. DOI: 10.4049/jimmunol.167.12.6869. View

12.

Geginat J, Sallusto F, Lanzavecchia A . Cytokine-driven proliferation and differentiation of human naive, central memory, and effector memory CD4(+) T cells. J Exp Med. 2001; 194(12):1711-9. PMC: 2193568. DOI: 10.1084/jem.194.12.1711. View

13.

Harbertson J, Biederman E, Bennett K, Kondrack R, Bradley L . Withdrawal of stimulation may initiate the transition of effector to memory CD4 cells. J Immunol. 2002; 168(3):1095-102. DOI: 10.4049/jimmunol.168.3.1095. View

14.

Kassiotis G, Garcia S, Simpson E, Stockinger B . Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nat Immunol. 2002; 3(3):244-50. DOI: 10.1038/ni766. View

15.

Goldrath A, Sivakumar P, Glaccum M, Kennedy M, Bevan M, Benoist C . Cytokine requirements for acute and Basal homeostatic proliferation of naive and memory CD8+ T cells. J Exp Med. 2002; 195(12):1515-22. PMC: 2193554. DOI: 10.1084/jem.20020033. View

16.

Tan J, Ernst B, Kieper W, Leroy E, Sprent J, Surh C . Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J Exp Med. 2002; 195(12):1523-32. PMC: 2193564. DOI: 10.1084/jem.20020066. View

17.

Kieper W, Tan J, Bondi-Boyd B, Gapin L, Sprent J, Ceredig R . Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of memory phenotype CD8+ T cells. J Exp Med. 2002; 195(12):1533-9. PMC: 2193553. DOI: 10.1084/jem.20020067. View

18.

Becker T, Wherry E, Boone D, Murali-Krishna K, Antia R, Ma A . Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J Exp Med. 2002; 195(12):1541-8. PMC: 2193552. DOI: 10.1084/jem.20020369. View

19.

Hildeman D, Zhu Y, Mitchell T, Bouillet P, Strasser A, Kappler J . Activated T cell death in vivo mediated by proapoptotic bcl-2 family member bim. Immunity. 2002; 16(6):759-67. DOI: 10.1016/s1074-7613(02)00322-9. View

20.

Dooms H, Abbas A . Life and death in effector T cells. Nat Immunol. 2002; 3(9):797-8. DOI: 10.1038/ni0902-797. View