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. 1991 Sep;74(1):78–85.

Loss of activation-induced CD45RO with maintenance of CD45RA expression during prolonged culture of T cells and NK cells.

H S Warren 1, L J Skipsey 1
PMCID: PMC1384675  PMID: 1834549

Abstract

The results of the present study show that activation-induced changes in CD45RA and CD45RO expression on T cells and natural killer (NK) cells are not unidirectional for all cells during a 5-week culture period. T cells and NK cells were generated from a resting subpopulation of peripheral blood mononuclear cells (PBMC) defined by sedimentation at Percoll high buoyant densities (p greater than 1.0640 g/ml) and unresponsiveness to IL-2. T cells were activated by a combination of PHA, sheep erythrocytes and IL-2-conditioned medium (IL-2-CM), and NK cells were activated by co-culture with gamma-irradiated malignant melanoma (MM-170) cells and IL-2-CM. Both T-cell and NK-cell cultures were maintained by subculture in IL-2-CM. NK cells and the CD45R(Abright)RO(dim/neg) subpopulation of T cells gained CD45RO following activation and this was accompanied by a two-fold decrease in CD45RA expression. In different cultures, CD45RO expression was not stable on 28-80% of T cells and 10-55% of NK cells. Cells with decreased CD45RO expression showed increased expression of CD45RA. Instability of CD45RO expression on cultured T cells and NK cells occurred at a time following the period of rapid cell growth when the cells were entering a quiescent phase. Both the CD4+ and CD8+ T-cell subpopulation showed similar changes in CD45 isoform expression. In contrast to the results obtained with the CD45R(Abright)RO(dim/neg) resting T cells, the CD45RO(bright)RA(dim/neg) subpopulation of resting T cells when activated and cultured under identical conditions retained CD45RO expression and remained CD45RAdim/neg. Thus a significant proportion of resting CD45R(Abright)RO(dim/neg) T cells is not related in a differentiation sequence to resting CD45RObrightRAdim/neg T cells, and therefore resting CD45RAbrightROdim/neg T cells and resting NK cells may be heterogeneous with respect to their activation history.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. 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]
  3. Bell E. B., Sparshott S. M. Interconversion of CD45R subsets of CD4 T cells in vivo. Nature. 1990 Nov 8;348(6297):163–166. doi: 10.1038/348163a0. [DOI] [PubMed] [Google Scholar]
  4. Brod S. A., Rudd C. E., Purvee M., Hafler D. A. Lymphokine regulation of CD45R expression on human T cell clones. J Exp Med. 1989 Dec 1;170(6):2147–2152. doi: 10.1084/jem.170.6.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Kristensson K., Dohlsten M., Fischer H., Ericsson P. O., Hedlund G., Sjögren H. O., Carlsson R. Phenotypical and functional differentiation of CD4+ CD45RA+ human T cells following polyclonal activation. Scand J Immunol. 1990 Sep;32(3):243–253. doi: 10.1111/j.1365-3083.1990.tb02917.x. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Nagler A., Lanier L. L., Cwirla S., Phillips J. H. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989 Nov 15;143(10):3183–3191. [PubMed] [Google Scholar]
  9. Richards S. J., Jones R. A., Roberts B. E., Patel D., Scott C. S. Relationships between 2H4 (CD45RA) and UCHL1 (CD45RO) expression by normal blood CD4+CD8-, CD4-CD8+, CD4-CD8dim+, CD3+CD4-CD8- and CD3-CD4-CD8- lymphocytes. Clin Exp Immunol. 1990 Jul;81(1):149–155. doi: 10.1111/j.1365-2249.1990.tb05306.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Rothstein D. M., Yamada A., Schlossman S. F., Morimoto C. Cyclic regulation of CD45 isoform expression in a long term human CD4+CD45RA+ T cell line. J Immunol. 1991 Feb 15;146(4):1175–1183. [PubMed] [Google Scholar]
  12. 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]
  13. Schwinzer R., Wonigeit K. Genetically determined lack of CD45R- T cells in healthy individuals. Evidence for a regulatory polymorphism of CD45R antigen expression. J Exp Med. 1990 May 1;171(5):1803–1808. doi: 10.1084/jem.171.5.1803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Thomas M. L., Lefrançois L. Differential expression of the leucocyte-common antigen family. Immunol Today. 1988 Oct;9(10):320–326. doi: 10.1016/0167-5699(88)91326-6. [DOI] [PubMed] [Google Scholar]
  15. Wallace D. L., Beverley P. C. Phenotypic changes associated with activation of CD45RA+ and CD45RO+ T cells. Immunology. 1990 Mar;69(3):460–467. [PMC free article] [PubMed] [Google Scholar]
  16. Warren H. S., Atkinson K., Pembrey R. G., Biggs J. C. Human bone marrow allograft recipients: production of, and responsiveness to, interleukin 2. J Immunol. 1983 Oct;131(4):1771–1775. [PubMed] [Google Scholar]
  17. Warren H. S., Bezos A. Heterogeneity in the activation requirements of T cells stimulated by phytohaemagglutinin. Immunology. 1987 Jun;61(2):167–172. [PMC free article] [PubMed] [Google Scholar]
  18. Warren H. S., Pembrey R. G. Cyclosporin inhibits a two-signal mechanism for the generation of cytotoxic NK-like cells, from small lymphocyte precursors. Immunol Lett. 1986 Mar;12(2-3):69–75. doi: 10.1016/0165-2478(86)90085-4. [DOI] [PubMed] [Google Scholar]
  19. Warren H. S. Resting (IL-2 non-responsive) precursors of human T cell receptor gamma delta-positive cells (TCR1 cells) are activated by a two signal process. Immunol Cell Biol. 1989 Apr;67(Pt 2):121–126. doi: 10.1038/icb.1989.17. [DOI] [PubMed] [Google Scholar]
  20. Warren H. S., Skipsey L. J. Phenotypic analysis of a resting subpopulation of human peripheral blood NK cells: the FcR gamma III (CD16) molecule and NK cell differentiation. Immunology. 1991 Jan;72(1):150–157. [PMC free article] [PubMed] [Google Scholar]
  21. Zola H., Melo J. V., Zowtyj H. N., Nikoloutsopoulos A., Skinner J. The leukocyte-common antigen (CD45) complex and B-lymphocyte activation. Hum Immunol. 1990 Apr;27(4):368–377. doi: 10.1016/0198-8859(90)90087-6. [DOI] [PubMed] [Google Scholar]

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