Newly Generated CD4 T Cells in Aged Animals Do Not Exhibit Age-related Defects in Response to Antigen

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2005 Mar 23

PMID 15781577

Citations 59

Authors

Laura Haynes

Sheri M Eaton

Eve M Burns

Troy D Randall

Susan L Swain

Affiliations

Soon will be listed here.

Abstract

Using a T cell receptor transgenic (TCR Tg) mouse model, we have shown that TCR Tg CD4 cells from aged mice retain a naive phenotype, but exhibit reduced proliferation and IL-2 production in response to the antigen compared with cells from young mice. We hypothesize that age-related decreases in T cell function may be partly related to the age of the T cells. Because thymic output is decreased with age, peripheral T cells in older individuals are likely to be older than those in younger individuals. To investigate this possibility, we have manipulated the age of CD4 T cells in the periphery of young and aged mice. The production of new T cells was induced by depleting peripheral CD4 T cells or by creating bone marrow chimeras. In both young and aged individuals where we induced the production of new T cells, these newly generated cells exhibited robust responses to antigen ex vivo and in vivo, exhibiting good expansion, IL-2 production, and cognate helper function. Our results suggest that age-related defects in response to antigenic stimulation, in part, are caused by the age of the CD4 T cells.

Citing Articles

"An Intrinsic Program Determines Key Age-Associated Changes in Adaptive Immunity that Limit Response to Non-Pathogens.".

Swain S, Kugler-Umana O, Tonkonogy S Front Aging. 2022; 2.

PMID: 35382063 PMC: 8979546. DOI: 10.3389/fragi.2021.701900.

Understanding the Heterogeneous Population of Age-Associated B Cells and Their Contributions to Autoimmunity and Immune Response to Pathogens.

Kugler-Umana O, Devarajan P, Swain S Crit Rev Immunol. 2021; 40(4):297-309.

PMID: 33426819 PMC: 8118092. DOI: 10.1615/CritRevImmunol.2020034934.

COPD as a Disease of Immunosenescence.

Cho W, Lee C, Kim L Yonsei Med J. 2019; 60(5):407-413.

PMID: 31016901 PMC: 6479124. DOI: 10.3349/ymj.2019.60.5.407.

The Pivotal Role of Thymus in Atherosclerosis Mediated by Immune and Inflammatory Response.

Dai X, Zhang D, Wang C, Wu Z, Liang C Int J Med Sci. 2018; 15(13):1555-1563.

PMID: 30443178 PMC: 6216065. DOI: 10.7150/ijms.27238.

Lymph nodes as barriers to T-cell rejuvenation in aging mice and nonhuman primates.

Thompson H, Smithey M, Uhrlaub J, Jeftic I, Jergovic M, White S Aging Cell. 2018; 18(1):e12865.

PMID: 30430748 PMC: 6351843. DOI: 10.1111/acel.12865.

References

Kaye J, HSU M, Sauron M, Jameson S, Gascoigne N, Hedrick S . Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature. 1989; 341(6244):746-9. DOI: 10.1038/341746a0. View

Glezen W, Decker M, Joseph S, Mercready Jr R . Acute respiratory disease associated with influenza epidemics in Houston, 1981-1983. J Infect Dis. 1987; 155(6):1119-26. DOI: 10.1093/infdis/155.6.1119. View

Flescher E, Ledbetter J, Schieven G, Fossum D, Dang H, Ogawa N . Longitudinal exposure of human T lymphocytes to weak oxidative stress suppresses transmembrane and nuclear signal transduction. J Immunol. 1994; 153(11):4880-9. View

Dubey C, Croft M, Swain S . Costimulatory requirements of naive CD4+ T cells. ICAM-1 or B7-1 can costimulate naive CD4 T cell activation but both are required for optimum response. J Immunol. 1995; 155(1):45-57. View

Lohmiller J, Roellich K, Toledano A, Rabinovitch P, WOLF N, Grossmann A . Aged murine T-lymphocytes are more resistant to oxidative damage due to the predominance of the cells possessing the memory phenotype. J Gerontol A Biol Sci Med Sci. 1996; 51(2):B132-40. DOI: 10.1093/gerona/51a.2.b132. View

Miller R . The aging immune system: primer and prospectus. Science. 1996; 273(5271):70-4. DOI: 10.1126/science.273.5271.70. View

Garvy B, Harmsen A . The role of T cells in infection-driven interstitial pneumonia after bone marrow transplantation in mice. Transplantation. 1996; 62(4):517-25. DOI: 10.1097/00007890-199608270-00015. View

Linton P, Haynes L, Klinman N, Swain S . Antigen-independent changes in naive CD4 T cells with aging. J Exp Med. 1996; 184(5):1891-900. PMC: 2192899. DOI: 10.1084/jem.184.5.1891. View

Berzins S, Boyd R, Miller J . The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool. J Exp Med. 1998; 187(11):1839-48. PMC: 2212318. DOI: 10.1084/jem.187.11.1839. View

10.

Haynes L, Linton P, Eaton S, Tonkonogy S, Swain S . Interleukin 2, but not other common gamma chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice. J Exp Med. 1999; 190(7):1013-24. PMC: 2195647. DOI: 10.1084/jem.190.7.1013. View

11.

Eaton S, Burns E, Kusser K, Randall T, Haynes L . Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses. J Exp Med. 2004; 200(12):1613-22. PMC: 2211991. DOI: 10.1084/jem.20041395. View

12.

Tamir A, Eisenbraun M, Garcia G, Miller R . Age-dependent alterations in the assembly of signal transduction complexes at the site of T cell/APC interaction. J Immunol. 2000; 165(3):1243-51. DOI: 10.4049/jimmunol.165.3.1243. View

13.

Garcia G, Miller R . Single-cell analyses reveal two defects in peptide-specific activation of naive T cells from aged mice. J Immunol. 2001; 166(5):3151-7. DOI: 10.4049/jimmunol.166.5.3151. View

14.

Haynes L, Eaton S, Swain S . Effect of age on naive CD4 responses: impact on effector generation and memory development. Springer Semin Immunopathol. 2002; 24(1):53-60. DOI: 10.1007/s00281-001-0095-2. View

15.

Grayson J, Harrington L, Lanier J, Wherry E, Ahmed R . Differential sensitivity of naive and memory CD8+ T cells to apoptosis in vivo. J Immunol. 2002; 169(7):3760-70. DOI: 10.4049/jimmunol.169.7.3760. View

16.

Kusser K, Randall T . Simultaneous detection of EGFP and cell surface markers by fluorescence microscopy in lymphoid tissues. J Histochem Cytochem. 2002; 51(1):5-14. DOI: 10.1177/002215540305100102. View

17.

Li L, Hsu H, Grizzle W, Stockard C, Ho K, Lott P . Cellular mechanism of thymic involution. Scand J Immunol. 2003; 57(5):410-22. DOI: 10.1046/j.1365-3083.2003.01206.x. View

18.

Haynes L, Eaton S, Burns E, Randall T, Swain S . CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly. Proc Natl Acad Sci U S A. 2003; 100(25):15053-8. PMC: 299903. DOI: 10.1073/pnas.2433717100. View

19.

Linton P, Dorshkind K . Age-related changes in lymphocyte development and function. Nat Immunol. 2004; 5(2):133-9. DOI: 10.1038/ni1033. View

20.

Haynes L, Eaton S, Burns E, Rincon M, Swain S . Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo. J Immunol. 2004; 172(9):5194-9. PMC: 3752606. DOI: 10.4049/jimmunol.172.9.5194. View