Lymphopenia and Mechanisms of T-Cell Regeneration

Overview

Journal Cell tissue biol

Date 2022 Aug 15

PMID 35967247

Authors

E V Saidakova

Affiliations

Soon will be listed here.

Abstract

Chronic lymphopenia, in particular, T-lymphocyte deficiency, increases the risk of death from cancer, cardiovascular and respiratory diseases and serves as a risk factor for a severe course and poor outcome of infectious diseases such as COVID-19. The regeneration of T-lymphocytes is a complex multilevel process, many questions of which still remain unanswered. The present review considers two main pathways of increasing the T-cell number in lymphopenia: production in the thymus and homeostatic proliferation in the periphery. Literature data on the signals that regulate each pathway are summarized. Their contribution to the quantitative and qualitative restoration of the immune cell pool is analyzed. The features of CD4 and CD8 T-lymphocytes' regeneration are considered.

References

Schulze-Koops H . Lymphopenia and autoimmune diseases. Arthritis Res Ther. 2004; 6(4):178-80. PMC: 464928. DOI: 10.1186/ar1208. View

Raff M . Social controls on cell survival and cell death. Nature. 1992; 356(6368):397-400. DOI: 10.1038/356397a0. View

Harris J, Hazenberg M, Poulin J, Higuera-Alhino D, Schmidt D, Gotway M . Multiparameter evaluation of human thymic function: interpretations and caveats. Clin Immunol. 2005; 115(2):138-46. DOI: 10.1016/j.clim.2004.12.008. View

King C, Ilic A, Koelsch K, Sarvetnick N . Homeostatic expansion of T cells during immune insufficiency generates autoimmunity. Cell. 2004; 117(2):265-77. DOI: 10.1016/s0092-8674(04)00335-6. View

Fry T, Mackall C . Interleukin-7: master regulator of peripheral T-cell homeostasis?. Trends Immunol. 2001; 22(10):564-71. DOI: 10.1016/s1471-4906(01)02028-2. View

Min B, Yamane H, Hu-Li J, Paul W . Spontaneous and homeostatic proliferation of CD4 T cells are regulated by different mechanisms. J Immunol. 2005; 174(10):6039-44. DOI: 10.4049/jimmunol.174.10.6039. View

Mackall C, Bare C, Granger L, Sharrow S, Titus J, Gress R . Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol. 1996; 156(12):4609-16. View

Masopust D, Vezys V, Marzo A, Lefrancois L . Preferential localization of effector memory cells in nonlymphoid tissue. Science. 2001; 291(5512):2413-7. DOI: 10.1126/science.1058867. View

Porter B, Scibelli P, Malek T . Control of T cell development in vivo by subdomains within the IL-7 receptor alpha-chain cytoplasmic tail. J Immunol. 2000; 166(1):262-9. DOI: 10.4049/jimmunol.166.1.262. View

10.

Forman S, Nocker P, Gallagher M, Zaia J, Wright C, Bolen J . Pattern of T cell reconstitution following allogeneic bone marrow transplantation for acute hematological malignancy. Transplantation. 1982; 34(2):96-8. DOI: 10.1097/00007890-198208000-00007. View

11.

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

12.

Datta S, Sarvetnick N . Lymphocyte proliferation in immune-mediated diseases. Trends Immunol. 2009; 30(9):430-8. DOI: 10.1016/j.it.2009.06.002. View

13.

Douek D, McFarland R, KEISER P, Gage E, Massey J, Haynes B . Changes in thymic function with age and during the treatment of HIV infection. Nature. 1999; 396(6712):690-5. DOI: 10.1038/25374. View

14.

Ge Q, Rao V, Cho B, Eisen H, Chen J . Dependence of lymphopenia-induced T cell proliferation on the abundance of peptide/ MHC epitopes and strength of their interaction with T cell receptors. Proc Natl Acad Sci U S A. 2001; 98(4):1728-33. PMC: 29325. DOI: 10.1073/pnas.98.4.1728. View

15.

Cosgrove D, Gray D, Dierich A, Kaufman J, Lemeur M, Benoist C . Mice lacking MHC class II molecules. Cell. 1991; 66(5):1051-66. DOI: 10.1016/0092-8674(91)90448-8. View

16.

Roux E, Starobinski M, Siegrist C, Helg C, Chapuis B, Roosnek E . Recovery of immune reactivity after T-cell-depleted bone marrow transplantation depends on thymic activity. Blood. 2000; 96(6):2299-303. View

17.

Ahmed R . Cutting edge: naive T cells masquerading as memory cells. J Immunol. 2000; 165(4):1733-7. DOI: 10.4049/jimmunol.165.4.1733. View

18.

Mackall C, Fleisher T, Brown M, Andrich M, Chen C, Feuerstein I . Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy. Blood. 1997; 89(10):3700-7. View

19.

Oehen S . Naïve cytotoxic T lymphocytes spontaneously acquire effector function in lymphocytopenic recipients: A pitfall for T cell memory studies?. Eur J Immunol. 1999; 29(2):608-14. DOI: 10.1002/(SICI)1521-4141(199902)29:02<608::AID-IMMU608>3.0.CO;2-A. View

20.

Enouz S, Carrie L, Merkler D, Bevan M, Zehn D . Autoreactive T cells bypass negative selection and respond to self-antigen stimulation during infection. J Exp Med. 2012; 209(10):1769-79. PMC: 3457731. DOI: 10.1084/jem.20120905. View