Abstract
A simple in vitro experimental system was devised to reflect the in vivo generation of a T cell anamnestic response so that T cell differentiation could be examined at the level of lymphokine gene expression. Comparison of neonatal and adult T cells revealed that both populations expressed the genes for interleukin 2 (IL-2) and its receptor, but only adult T cells were capable of transcribing mRNAs for IL-3, IL-4, IL-5, IL-6, interferon gamma, and granulocyte/macrophage colony-stimulating factor. However, neonatal T cells could be induced to undergo functional differentiation in vitro, thereby acquiring the capacity to express the lymphokine gene repertoire characteristic for adult T cells. These data suggest that the T cells generated from neonatal blood by a primary stimulation in vitro are functionally indistinguishable from the T cells in adult blood that presumably have undergone primary stimulation in vivo. Therefore, we propose that the term "memory cell" be applied to those T cells that can be identified by their differentiated state of inducible effector-lymphokine gene expression.
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- Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
- Andersson B., Skoglund A. C., Rönnholm M., Lindsten T., Lamon E. W., Collisson E. W., Walia A. S. Functional aspects of IgM and IgG Fc receptors on murine T lymphocytes. Immunol Rev. 1981;56:5–50. doi: 10.1111/j.1600-065x.1981.tb01046.x. [DOI] [PubMed] [Google Scholar]
- Anegón I., Cuturi M. C., Trinchieri G., Perussia B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med. 1988 Feb 1;167(2):452–472. doi: 10.1084/jem.167.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berek C., Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. Immunol Rev. 1987 Apr;96:23–41. doi: 10.1111/j.1600-065x.1987.tb00507.x. [DOI] [PubMed] [Google Scholar]
- Bertotto A., Gerli R., Lanfrancone L., Crupi S., Arcangeli C., Cernetti C., Spinozzi F., Rambotti P. Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody. Cell Immunol. 1990 May;127(2):247–259. doi: 10.1016/0008-8749(90)90130-j. [DOI] [PubMed] [Google Scholar]
- Beverley P. C. Is T-cell memory maintained by crossreactive stimulation? Immunol Today. 1990 Jun;11(6):203–205. doi: 10.1016/0167-5699(90)90083-l. [DOI] [PubMed] [Google Scholar]
- Brenner C. A., Tam A. W., Nelson P. A., Engleman E. G., Suzuki N., Fry K. E., Larrick J. W. Message amplification phenotyping (MAPPing): a technique to simultaneously measure multiple mRNAs from small numbers of cells. Biotechniques. 1989 Nov-Dec;7(10):1096–1103. [PubMed] [Google Scholar]
- Bryson Y. J., Winter H. S., Gard S. E., Fischer T. J., Stiehm E. R. Deficiency of immune interferon production by leukocytes of normal newborns. Cell Immunol. 1980 Sep 15;55(1):191–200. doi: 10.1016/0008-8749(80)90150-1. [DOI] [PubMed] [Google Scholar]
- Byrne J. A., Butler J. L., Cooper M. D. Differential activation requirements for virgin and memory T cells. J Immunol. 1988 Nov 15;141(10):3249–3257. [PubMed] [Google Scholar]
- Byrne J. A., Butler J. L., Reinherz E. L., Cooper M. D. Virgin and memory T cells have different requirements for activation via the CD2 molecule. Int Immunol. 1989;1(1):29–35. doi: 10.1093/intimm/1.1.29. [DOI] [PubMed] [Google Scholar]
- Cerottini J. C., Engers H. D., Macdonald H. R., Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med. 1974 Sep 1;140(3):703–717. doi: 10.1084/jem.140.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerottini J. C., MacDonald H. R. The cellular basis of T-cell memory. Annu Rev Immunol. 1989;7:77–89. doi: 10.1146/annurev.iy.07.040189.000453. [DOI] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Clement L. T., Yamashita N., Martin A. M. The functionally distinct subpopulations of human CD4+ helper/inducer T lymphocytes defined by anti-CD45R antibodies derive sequentially from a differentiation pathway that is regulated by activation-dependent post-thymic differentiation. J Immunol. 1988 Sep 1;141(5):1464–1470. [PubMed] [Google Scholar]
- Damle N. K., Doyle L. V. Ability of human T lymphocytes to adhere to vascular endothelial cells and to augment endothelial permeability to macromolecules is linked to their state of post-thymic maturation. J Immunol. 1990 Feb 15;144(4):1233–1240. [PubMed] [Google Scholar]
- Damle N. K., Doyle L. V., Bender J. R., Bradley E. C. Interleukin 2-activated human lymphocytes exhibit enhanced adhesion to normal vascular endothelial cells and cause their lysis. J Immunol. 1987 Mar 15;138(6):1779–1785. [PubMed] [Google Scholar]
- Geppert T. D., Lipsky P. E. Accessory cell independent proliferation of human T4 cells stimulated by immobilized monoclonal antibodies to CD3. J Immunol. 1987 Mar 15;138(6):1660–1666. [PubMed] [Google Scholar]
- Gerli R., Bertotto A., Crupi S., Arcangeli C., Marinelli I., Spinozzi F., Cernetti C., Angelella P., Rambotti P. Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule. J Immunol. 1989 Apr 15;142(8):2583–2589. [PubMed] [Google Scholar]
- Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
- Hafler D. A., Fox D. A., Benjamin D., Weiner H. L. Antigen reactive memory T cells are defined by Ta1. J Immunol. 1986 Jul 15;137(2):414–418. [PubMed] [Google Scholar]
- Hayward A. R., Lawton A. R. Induction of plasma cell differentiation of human fetal lymphocytes: evidence for functional immaturity of T and B cells. J Immunol. 1977 Oct;119(4):1213–1217. [PubMed] [Google Scholar]
- Horgan K. J., Van Seventer G. A., Shimizu Y., Shaw S. Hyporesponsiveness of "naive" (CD45RA+) human T cells to multiple receptor-mediated stimuli but augmentation of responses by co-stimuli. Eur J Immunol. 1990 May;20(5):1111–1118. doi: 10.1002/eji.1830200525. [DOI] [PubMed] [Google Scholar]
- Hoy C. A., Rice G. C., Kovacs M., Schimke R. T. Over-replication of DNA in S phase Chinese hamster ovary cells after DNA synthesis inhibition. J Biol Chem. 1987 Sep 5;262(25):11927–11934. [PubMed] [Google Scholar]
- Inaba K., Steinman R. M. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release. J Exp Med. 1984 Dec 1;160(6):1717–1735. doi: 10.1084/jem.160.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janossy G., Bofill M., Rowe D., Muir J., Beverley P. C. The tissue distribution of T lymphocytes expressing different CD45 polypeptides. Immunology. 1989 Apr;66(4):517–525. [PMC free article] [PubMed] [Google Scholar]
- Koyasu S., Lawton T., Novick D., Recny M. A., Siliciano R. F., Wallner B. P., Reinherz E. L. Role of interaction of CD2 molecules with lymphocyte function-associated antigen 3 in T-cell recognition of nominal antigen. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2603–2607. doi: 10.1073/pnas.87.7.2603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis D. B., Larsen A., Wilson C. B. Reduced interferon-gamma mRNA levels in human neonates. Evidence for an intrinsic T cell deficiency independent of other genes involved in T cell activation. J Exp Med. 1986 Apr 1;163(4):1018–1023. doi: 10.1084/jem.163.4.1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewis D. B., Prickett K. S., Larsen A., Grabstein K., Weaver M., Wilson C. B. Restricted production of interleukin 4 by activated human T cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9743–9747. doi: 10.1073/pnas.85.24.9743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackay C. R., Marston W. L., Dudler L. Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med. 1990 Mar 1;171(3):801–817. doi: 10.1084/jem.171.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuyama T., Anderson P., Daley J. F., Schlossman S., Morimoto C. CD4+CD45R+ cells are preferentially activated through the CD2 pathway. Eur J Immunol. 1988 Sep;18(9):1473–1476. doi: 10.1002/eji.1830180926. [DOI] [PubMed] [Google Scholar]
- Miyagawa Y., Sugita K., Komiyama A., Akabane T. Delayed in vitro immunoglobulin production by cord lymphocytes. Pediatrics. 1980 Mar;65(3):497–500. [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
- Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
- Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
- Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
- Papadogiannakis N., Johnsen S. A., Olding L. B. Monocyte-regulated hyporesponsiveness of human cord blood lymphocytes to OKT3-monoclonal-antibody-induced mitogenesis. Scand J Immunol. 1986 Jan;23(1):91–99. doi: 10.1111/j.1365-3083.1986.tb01946.x. [DOI] [PubMed] [Google Scholar]
- Patel S. S., Duby A. D., Thiele D. L., Lipsky P. E. Phenotypic and functional characterization of human T cell clones. J Immunol. 1988 Dec 1;141(11):3726–3736. [PubMed] [Google Scholar]
- Pistoia V., Zupo S., Corcione A., Roncella S., Matera L., Ghio R., Ferrarini M. Production of colony-stimulating activity by human natural killer cells: analysis of the conditions that influence the release and detection of colony-stimulating activity. Blood. 1989 Jul;74(1):156–164. [PubMed] [Google Scholar]
- Rappolee D. A., Mark D., Banda M. J., Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science. 1988 Aug 5;241(4866):708–712. doi: 10.1126/science.3041594. [DOI] [PubMed] [Google Scholar]
- Rappolee D. A., Werb Z. Secretory products of phagocytes. Curr Opin Immunol. 1988 Sep-Oct;1(1):47–55. doi: 10.1016/0952-7915(88)90050-7. [DOI] [PubMed] [Google Scholar]
- Rothstein D. M., Sohen S., Daley J. F., Schlossman S. F., Morimoto C. CD4+CD45RA+ and CD4+CD45RA- T cell subsets in man maintain distinct function and CD45RA expression persists on a subpopulation of CD45RA+ cells after activation with Con A. Cell Immunol. 1990 Sep;129(2):449–467. doi: 10.1016/0008-8749(90)90220-l. [DOI] [PubMed] [Google Scholar]
- Salmon M., Kitas G. D., Bacon P. A. Production of lymphokine mRNA by CD45R+ and CD45R- helper T cells from human peripheral blood and by human CD4+ T cell clones. J Immunol. 1989 Aug 1;143(3):907–912. [PubMed] [Google Scholar]
- Sanders M. E., Makgoba M. W., June C. H., Young H. A., Shaw S. Enhanced responsiveness of human memory T cells to CD2 and CD3 receptor-mediated activation. Eur J Immunol. 1989 May;19(5):803–808. doi: 10.1002/eji.1830190504. [DOI] [PubMed] [Google Scholar]
- Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
- Sanders M. E., Makgoba M. W., 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. doi: 10.1016/0167-5699(88)91212-1. [DOI] [PubMed] [Google Scholar]
- Schraven B., Roux M., Hutmacher B., Meuer S. C. Triggering of the alternative pathway of human T cell activation involves members of the T 200 family of glycoproteins. Eur J Immunol. 1989 Feb;19(2):397–403. doi: 10.1002/eji.1830190226. [DOI] [PubMed] [Google Scholar]
- Serra H. M., Krowka J. F., Ledbetter J. A., Pilarski L. M. Loss of CD45R (Lp220) represents a post-thymic T cell differentiation event. J Immunol. 1988 Mar 1;140(5):1435–1441. [PubMed] [Google Scholar]
- Smith S. H., Brown M. H., Rowe D., Callard R. E., Beverley P. C. Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology. 1986 May;58(1):63–70. [PMC free article] [PubMed] [Google Scholar]
- Taylor S., Bryson Y. J. Impaired production of gamma-interferon by newborn cells in vitro is due to a functionally immature macrophage. J Immunol. 1985 Mar;134(3):1493–1497. [PubMed] [Google Scholar]
- Tedder T. F., Clement L. T., Cooper M. D. Human lymphocyte differentiation antigens HB-10 and HB-11. I. Ontogeny of antigen expression. J Immunol. 1985 May;134(5):2983–2988. [PubMed] [Google Scholar]
- Tedder T. F., Matsuyama T., Rothstein D., Schlossman S. F., Morimoto C. Human antigen-specific memory T cells express the homing receptor (LAM-1) necessary for lymphocyte recirculation. Eur J Immunol. 1990 Jun;20(6):1351–1355. doi: 10.1002/eji.1830200622. [DOI] [PubMed] [Google Scholar]
- Thiele D. L., Kurosaka M., Lipsky P. E. Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. J Immunol. 1983 Nov;131(5):2282–2290. [PubMed] [Google Scholar]
- Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
- Turka L. A., Ledbetter J. A., Lee K., June C. H., Thompson C. B. CD28 is an inducible T cell surface antigen that transduces a proliferative signal in CD3+ mature thymocytes. J Immunol. 1990 Mar 1;144(5):1646–1653. [PubMed] [Google Scholar]
- Wilson C. B., Westall J., Johnston L., Lewis D. B., Dower S. K., Alpert A. R. Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies. J Clin Invest. 1986 Mar;77(3):860–867. doi: 10.1172/JCI112383. [DOI] [PMC free article] [PubMed] [Google Scholar]