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J Exp Med. 1994 Apr 1; 179(4): 1127–1135.
PMCID: PMC2191431

Turnover of naive- and memory-phenotype T cells


On the basis of their surface markers, T lymphocytes are divided into subsets of "naive" and "memory cells". We have defined the interrelationship and relative life spans of naive and memory T cells by examining the surface markers on murine T cells incorporating bromodeoxyuridine, a DNA precursor, given in the drinking water. Three findings are reported. First, using a new method we show that the release of newly formed naive T cells from the unmanipulated thymus is very low (confirming the findings of others with surgical approaches). Second, in thymectomized mice, T cells with a naive phenotype remain in interphase for prolonged periods; however, some of these cells divide and retain (or regain) their "naive" markers. Third, most T cells with a memory phenotype divide rapidly, but others remain in interphase for many weeks. Collectively, the data indicate that long-lived T cells have multiple phenotypes and contain a mixture of memory cells, naive (virgin) cells, and memory cells masquerading as naive cells.

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Selected References

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  • Sanders ME, Makgoba MW, Shaw S. Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today. 1988 Jul-Aug;9(7-8):195–199. [PubMed]
  • Powrie F, Mason D. Phenotypic and functional heterogeneity of CD4+ T cells. Immunol Today. 1988 Sep;9(9):274–277. [PubMed]
  • Mackay CR. Immunological memory. Adv Immunol. 1993;53:217–265. [PubMed]
  • Bell EB. Function of CD4 T cell subsets in vivo: expression of CD45R isoforms. Semin Immunol. 1992 Feb;4(1):43–50. [PubMed]
  • Hayakawa K, Hardy RR. Murine CD4+ T-cell subsets. Immunol Rev. 1991 Oct;123:145–168. [PubMed]
  • Budd RC, Cerottini JC, Horvath C, Bron C, Pedrazzini T, Howe RC, MacDonald HR. Distinction of virgin and memory T lymphocytes. Stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. J Immunol. 1987 May 15;138(10):3120–3129. [PubMed]
  • Stout RD, Suttles J. T cells bearing the CD44hi "memory" phenotype display characteristics of activated cells in G1 stage of cell cycle. Cell Immunol. 1992 May;141(2):433–443. [PubMed]
  • Picker LJ, Butcher EC. Physiological and molecular mechanisms of lymphocyte homing. Annu Rev Immunol. 1992;10:561–591. [PubMed]
  • Swain SL, Bradley LM, Croft M, Tonkonogy S, Atkins G, Weinberg AD, Duncan DD, Hedrick SM, Dutton RW, Huston G. Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development. Immunol Rev. 1991 Oct;123:115–144. [PubMed]
  • von Boehmer H, Hafen K. The life span of naive alpha/beta T cells in secondary lymphoid organs. J Exp Med. 1993 Apr 1;177(4):891–896. [PMC free article] [PubMed]
  • Sprent J. Lifespans of naive, memory and effector lymphocytes. Curr Opin Immunol. 1993 Jun;5(3):433–438. [PubMed]
  • De Paoli P, Battistin S, Santini GF. Age-related changes in human lymphocyte subsets: progressive reduction of the CD4 CD45R (suppressor inducer) population. Clin Immunol Immunopathol. 1988 Sep;48(3):290–296. [PubMed]
  • Lerner A, Yamada T, Miller RA. Pgp-1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A. Eur J Immunol. 1989 Jun;19(6):977–982. [PubMed]
  • Ernst DN, Hobbs MV, Torbett BE, Glasebrook AL, Rehse MA, Bottomly K, Hayakawa K, Hardy RR, Weigle WO. Differences in the expression profiles of CD45RB, Pgp-1, and 3G11 membrane antigens and in the patterns of lymphokine secretion by splenic CD4+ T cells from young and aged mice. J Immunol. 1990 Sep 1;145(5):1295–1302. [PubMed]
  • Ernst DN, Weigle WO, Noonan DJ, McQuitty DN, Hobbs MV. The age-associated increase in IFN-gamma synthesis by mouse CD8+ T cells correlates with shifts in the frequencies of cell subsets defined by membrane CD44, CD45RB, 3G11, and MEL-14 expression. J Immunol. 1993 Jul 15;151(2):575–587. [PubMed]
  • Bell EB, Sparshott SM, Drayson MT, Ford WL. The stable and permanent expansion of functional T lymphocytes in athymic nude rats after a single injection of mature T cells. J Immunol. 1987 Sep 1;139(5):1379–1384. [PubMed]
  • Rocha B, Dautigny N, Pereira P. Peripheral T lymphocytes: expansion potential and homeostatic regulation of pool sizes and CD4/CD8 ratios in vivo. Eur J Immunol. 1989 May;19(5):905–911. [PubMed]
  • Sprent J, Schaefer M, Hurd M, Surh CD, Ron Y. Mature murine B and T cells transferred to SCID mice can survive indefinitely and many maintain a virgin phenotype. J Exp Med. 1991 Sep 1;174(3):717–728. [PMC free article] [PubMed]
  • Gowans JL, Uhr JW. The carriage of immunological memory by small lymphocytes in the rat. J Exp Med. 1966 Nov 1;124(5):1017–1030. [PMC free article] [PubMed]
  • Gray D. The dynamics of immunological memory. Semin Immunol. 1992 Feb;4(1):29–34. [PubMed]
  • Mackay CR, Marston WL, Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990 Mar 1;171(3):801–817. [PMC free article] [PubMed]
  • Michie CA, McLean A, Alcock C, Beverley PC. Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature. 1992 Nov 19;360(6401):264–265. [PubMed]
  • Penit C. In vivo thymocyte maturation. BUdR labeling of cycling thymocytes and phenotypic analysis of their progeny support the single lineage model. J Immunol. 1986 Oct 1;137(7):2115–2121. [PubMed]
  • Förster I, Rajewsky K. The bulk of the peripheral B-cell pool in mice is stable and not rapidly renewed from the bone marrow. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4781–4784. [PMC free article] [PubMed]
  • Carayon P, Bord A. Identification of DNA-replicating lymphocyte subsets using a new method to label the bromo-deoxyuridine incorporated into the DNA. J Immunol Methods. 1992 Mar 4;147(2):225–230. [PubMed]
  • Kosaka H, Surh CD, Sprent J. Stimulation of mature unprimed CD8+ T cells by semiprofessional antigen-presenting cells in vivo. J Exp Med. 1992 Nov 1;176(5):1291–1302. [PMC free article] [PubMed]
  • Röpke C, Hougen HP, Everett NB. Long-lived T and B lymphocytes in the bone marrow and thoracic duct lymph of the mouse. Cell Immunol. 1975 Jan;15(1):82–93. [PubMed]
  • Egerton M, Scollay R, Shortman K. Kinetics of mature T-cell development in the thymus. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2579–2582. [PMC free article] [PubMed]
  • Huesmann M, Scott B, Kisielow P, von Boehmer H. Kinetics and efficacy of positive selection in the thymus of normal and T cell receptor transgenic mice. Cell. 1991 Aug 9;66(3):533–540. [PubMed]
  • Weissman IL. Thymus cell migration. J Exp Med. 1967 Aug 1;126(2):291–304. [PMC free article] [PubMed]
  • Scollay RG, Butcher EC, Weissman IL. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol. 1980 Mar;10(3):210–218. [PubMed]
  • Kelly KA, Scollay R. Analysis of recent thymic emigrants with subset- and maturity-related markers. Int Immunol. 1990;2(5):419–425. [PubMed]
  • Yang CP, Bell EB. Functional maturation of recent thymic emigrants in the periphery: development of alloreactivity correlates with the cyclic expression of CD45RC isoforms. Eur J Immunol. 1992 Sep;22(9):2261–2269. [PubMed]
  • Hosseinzadeh H, Goldschneider I. Recent thymic emigrants in the rat express a unique antigenic phenotype and undergo post-thymic maturation in peripheral lymphoid tissues. J Immunol. 1993 Mar 1;150(5):1670–1679. [PubMed]
  • Rocha B, Penit C, Baron C, Vasseur F, Dautigny N, Freitas AA. Accumulation of bromodeoxyuridine-labeled cells in central and peripheral lymphoid organs: minimal estimates of production and turnover rates of mature lymphocytes. Eur J Immunol. 1990 Aug;20(8):1697–1708. [PubMed]
  • Mobley JL, Dailey MO. Regulation of adhesion molecule expression by CD8 T cells in vivo. I. Differential regulation of gp90MEL-14 (LECAM-1), Pgp-1, LFA-1, and VLA-4 alpha during the differentiation of cytotoxic T lymphocytes induced by allografts. J Immunol. 1992 Apr 15;148(8):2348–2356. [PubMed]
  • Ernst DN, Weigle WO, Hobbs MV. Aging and lymphokine production by T cell subsets. Stem Cells. 1993 Nov;11(6):487–498. [PubMed]
  • Strober S. Immune function cell surface characteristics and maturation of B cell subpopulations. Transplant Rev. 1975;24:84–112. [PubMed]
  • Schittek B, Rajewsky K. Maintenance of B-cell memory by long-lived cells generated from proliferating precursors. Nature. 1990 Aug 23;346(6286):749–751. [PubMed]

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