Abstract
Healthy young (< 40 years) and elderly (< 60 years) adults were immunized with the 1992-1993 preparation of trivalent influenza vaccine, and changes in CD45 isoform expression on peripheral blood lymphocytes were measured in the pre- and postvaccination periods. Fluorescence-activated cell sorter analysis was used to study T-cell subsets in fresh peripheral blood lymphocytes (day 0) and after 6 days of culture with live influenza virus. We have reported previously that the interleukin-2 response to the stimulating strain of virus, A/Texas/16/89, did not decline until 26 weeks postvaccination. In ex vivo CD4+ subsets, this interleukin-2 response was paralleled by a > 10% increase in the proportion of cells expressing the CD45RO+ phenotype following vaccination (p < 0.0001). In vitro stimulation had no effect on CD4+ subsets prior to vaccination but, after vaccination, was associated with a > 10% increase in CD45RA+RO+ cells (P < 0.0001). In addition, we have identified a change in the population of cells that express a CD45 isoform that is neither CD45RA nor CD45RO (CD45RA-RO-). At 26 weeks postvaccination, the proportion of CD45RA-RO- cells in ex vivo CD4+ peripheral blood mononuclear cells increased by approximately 15% from that measured at the earlier postvaccination time points (P < 0.0001). In vitro stimulation with influenza virus resulted in a further 20% increase in the proportion of CD45RA-RO- cells (P < 0.0001). The CD45RA-RO- phenotype may identify a population of cells undergoing apoptosis (programmed cell death) that limits the duration of helper T-cell (CD4+) memory after vaccination.
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Selected References
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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]
- Akbar A. N., Timms A., Janossy G. Cellular events during memory T-cell activation in vitro: the UCHL1 (180,000 MW) determinant is newly synthesized after mitosis. Immunology. 1989 Feb;66(2):213–218. [PMC free article] [PubMed] [Google Scholar]
- Arthur R. P., Mason D. T cells that help B cell responses to soluble antigen are distinguishable from those producing interleukin 2 on mitogenic or allogeneic stimulation. J Exp Med. 1986 Apr 1;163(4):774–786. doi: 10.1084/jem.163.4.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bettens F., Walker C., Gauchat J. F., Gauchat D., Wyss T., Pichler W. J. Lymphokine gene expression related to CD4 T cell subset (CD45R/CDw29) phenotype conversion. Eur J Immunol. 1989 Sep;19(9):1569–1574. doi: 10.1002/eji.1830190908. [DOI] [PubMed] [Google Scholar]
- Budd R. C., Cerottini J. C., MacDonald H. R. Selectively increased production of interferon-gamma by subsets of Lyt-2+ and L3T4+ T cells identified by expression of Pgp-1. J Immunol. 1987 Jun 1;138(11):3583–3586. [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]
- Deans J. P., Boyd A. W., Pilarski L. M. Transitions from high to low molecular weight isoforms of CD45 (T200) involve rapid activation of alternate mRNA splicing and slow turnover of surface CD45R. J Immunol. 1989 Aug 15;143(4):1233–1238. [PubMed] [Google Scholar]
- Deans J. P., Serra H. M., Shaw J., Shen Y. J., Torres R. M., Pilarski L. M. Transient accumulation and subsequent rapid loss of messenger RNA encoding high molecular mass CD45 isoforms after T cell activation. J Immunol. 1992 Mar 15;148(6):1898–1905. [PubMed] [Google Scholar]
- Deans J. P., Wilkins J. A., Caixia S., Pruski E., Pilarski L. M. Prolonged expression of high molecular mass CD45RA isoform during the differentiation of human progenitor thymocytes to CD3+ cells in vitro. J Immunol. 1991 Dec 15;147(12):4060–4068. [PubMed] [Google Scholar]
- Erkeller-Yuksel F. M., Deneys V., Yuksel B., Hannet I., Hulstaert F., Hamilton C., Mackinnon H., Stokes L. T., Munhyeshuli V., Vanlangendonck F. Age-related changes in human blood lymphocyte subpopulations. J Pediatr. 1992 Feb;120(2 Pt 1):216–222. doi: 10.1016/s0022-3476(05)80430-5. [DOI] [PubMed] [Google Scholar]
- Lee W. T., Yin X. M., Vitetta E. S. Functional and ontogenetic analysis of murine CD45Rhi and CD45Rlo CD4+ T cells. J Immunol. 1990 May 1;144(9):3288–3295. [PubMed] [Google Scholar]
- Luqman M., Bottomly K. Activation requirements for CD4+ T cells differing in CD45R expression. J Immunol. 1992 Oct 1;149(7):2300–2306. [PubMed] [Google Scholar]
- McElhaney J. E., Meneilly G. S., Beattie B. L., Helgason C. D., Lee S. F., Devine R. D., Bleackley R. C. The effect of influenza vaccination on IL2 production in healthy elderly: implications for current vaccination practices. J Gerontol. 1992 Jan;47(1):M3–M8. doi: 10.1093/geronj/47.1.m3. [DOI] [PubMed] [Google Scholar]
- McElhaney J. E., Meneilly G. S., Lechelt K. E., Bleackley R. C. Split-virus influenza vaccines: do they provide adequate immunity in the elderly? J Gerontol. 1994 Mar;49(2):M37–M43. doi: 10.1093/geronj/49.2.m37. [DOI] [PubMed] [Google Scholar]
- McElhaney J. E., Pinkoski M. J., Meneilly G. S. Changes in CD45 isoform expression after influenza vaccination. Mech Ageing Dev. 1993 Jun;69(1-2):79–91. doi: 10.1016/0047-6374(93)90073-z. [DOI] [PubMed] [Google Scholar]
- Merkenschlager M., Terry L., Edwards R., Beverley P. C. Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation. Eur J Immunol. 1988 Nov;18(11):1653–1661. doi: 10.1002/eji.1830181102. [DOI] [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]
- Oravecz T., Monostori E., Kurucz E., Takács L., Andó I. CD3-induced T-cell proliferation and interleukin-2 secretion is modulated by the CD45 antigen. Scand J Immunol. 1991 Nov;34(5):531–537. doi: 10.1111/j.1365-3083.1991.tb01576.x. [DOI] [PubMed] [Google Scholar]
- Pilarski L. M., Yacyshyn B. R., Jensen G. S., Pruski E., Pabst H. F. Beta 1 integrin (CD29) expression on human postnatal T cell subsets defined by selective CD45 isoform expression. J Immunol. 1991 Aug 1;147(3):830–837. [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., 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]
- 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]
- Tough D. F., Sprent J. Turnover of naive- and memory-phenotype T cells. J Exp Med. 1994 Apr 1;179(4):1127–1135. doi: 10.1084/jem.179.4.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Xu X., Beckman I., Ahern M., Bradley J. A comprehensive analysis of peripheral blood lymphocytes in healthy aged humans by flow cytometry. Immunol Cell Biol. 1993 Dec;71(Pt 6):549–557. doi: 10.1038/icb.1993.61. [DOI] [PubMed] [Google Scholar]