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. 1995 May;95(5):2054–2060. doi: 10.1172/JCI117891

Altered representation of naive and memory CD8 T cell subsets in HIV-infected children.

R L Rabin 1, M Roederer 1, Y Maldonado 1, A Petru 1, L A Herzenberg 1, L A Herzenberg 1
PMCID: PMC295792  PMID: 7738172

Abstract

CD8 T cells are divided into naive and memory subsets according to both function and phenotype. In HIV-negative children, the naive subset is present at high frequencies, whereas memory cells are virtually absent. Previous studies have shown that the overall number of CD8 T cells does not decrease in HIV-infected children. In studies here, we use multiparameter flow cytometry to distinguish naive from memory CD8 T cells based on expression of CD11a, CD45RA, and CD62L. With this methodology, we show that within the CD8 T cell population, the naive subset decreases markedly (HIV+ vs. HIV-, 190 vs. 370 cells/microliter; P < or = 0.003), and that there is a reciprocal increase in memory cells, such that the total CD8 T cell counts remained unchanged (800 vs. 860 cells/microliter; P < or = 0.76). In addition, we show that for HIV-infected children, the naive CD8 T cell and total CD4 T cell counts correlate (chi 2 P < or = 0.001). This correlated loss suggests that the loss of naive CD8 T cells in HIV infection may contribute to the defects in cell-mediated immunity which become progressively worse as the HIV disease progresses and CD4 counts decrease.

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Selected References

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

  1. 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]
  2. Bonyhadi M. L., Rabin L., Salimi S., Brown D. A., Kosek J., McCune J. M., Kaneshima H. HIV induces thymus depletion in vivo. Nature. 1993 Jun 24;363(6431):728–732. doi: 10.1038/363728a0. [DOI] [PubMed] [Google Scholar]
  3. Borkowsky W., Moore T., Krasinski K., Ajuang-Simbiri K. O., Holzman R. Evolution of phenotypic memory T cells in HIV-1 infected infants and children. Clin Immunol Immunopathol. 1992 Jun;63(3):280–284. doi: 10.1016/0090-1229(92)90234-f. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Church J. A., Costin G., Brooks J. Immune functions in children treated with biosynthetic growth hormone. J Pediatr. 1989 Sep;115(3):420–423. doi: 10.1016/s0022-3476(89)80845-5. [DOI] [PubMed] [Google Scholar]
  6. Clement L. T. Isoforms of the CD45 common leukocyte antigen family: markers for human T-cell differentiation. J Clin Immunol. 1992 Jan;12(1):1–10. doi: 10.1007/BF00918266. [DOI] [PubMed] [Google Scholar]
  7. Cook R. T., Waldschmidt T. J., Ballas Z. K., Cook B. L., Booth B. M., Stewart B. C., Garvey M. J. Fine T-cell subsets in alcoholics as determined by the expression of L-selectin, leukocyte common antigen, and beta-integrin. Alcohol Clin Exp Res. 1994 Feb;18(1):71–80. doi: 10.1111/j.1530-0277.1994.tb00883.x. [DOI] [PubMed] [Google Scholar]
  8. Froebel K. S., Doherty K. V., Whitelaw J. A., Hague R. A., Mok J. Y., Bird A. G. Increased expression of the CD45RO (memory) antigen on T cells in HIV-infected children. AIDS. 1991 Jan;5(1):97–99. doi: 10.1097/00002030-199101000-00015. [DOI] [PubMed] [Google Scholar]
  9. Froebel K. S., Doherty K. V., Whitelaw J. A., Hague R. A., Mok J. Y., Bird A. G. Increased expression of the CD45RO (memory) antigen on T cells in HIV-infected children. AIDS. 1991 Jan;5(1):97–99. doi: 10.1097/00002030-199101000-00015. [DOI] [PubMed] [Google Scholar]
  10. Giorgi J. V., Detels R. T-cell subset alterations in HIV-infected homosexual men: NIAID Multicenter AIDS cohort study. Clin Immunol Immunopathol. 1989 Jul;52(1):10–18. doi: 10.1016/0090-1229(89)90188-8. [DOI] [PubMed] [Google Scholar]
  11. Gray D. Immunological memory. Annu Rev Immunol. 1993;11:49–77. doi: 10.1146/annurev.iy.11.040193.000405. [DOI] [PubMed] [Google Scholar]
  12. Mackewicz C., Levy J. A. CD8+ cell anti-HIV activity: nonlytic suppression of virus replication. AIDS Res Hum Retroviruses. 1992 Jun;8(6):1039–1050. doi: 10.1089/aid.1992.8.1039. [DOI] [PubMed] [Google Scholar]
  13. Okumura M., Fujii Y., Inada K., Nakahara K., Matsuda H. Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells. J Immunol. 1993 Jan 15;150(2):429–437. [PubMed] [Google Scholar]
  14. Okumura M., Fujii Y., Takeuchi Y., Inada K., Nakahara K., Matsuda H. Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population. Eur J Immunol. 1993 May;23(5):1057–1063. doi: 10.1002/eji.1830230512. [DOI] [PubMed] [Google Scholar]
  15. Picker L. J., Treer J. R., Ferguson-Darnell B., Collins P. A., Buck D., Terstappen L. W. Control of lymphocyte recirculation in man. I. Differential regulation of the peripheral lymph node homing receptor L-selectin on T cells during the virgin to memory cell transition. J Immunol. 1993 Feb 1;150(3):1105–1121. [PubMed] [Google Scholar]
  16. Prince H. E., Jensen E. R. Three-color cytofluorometric analysis of CD8 cell subsets in HIV-1 infection. J Acquir Immune Defic Syndr. 1991;4(12):1227–1232. [PubMed] [Google Scholar]
  17. Prince H. E., Kleinman S., Czaplicki C., John J., Williams A. E. Interrelationships between serologic markers of immune activation and T lymphocyte subsets in HIV infection. J Acquir Immune Defic Syndr. 1990;3(5):525–530. [PubMed] [Google Scholar]
  18. Reddy M. M., Grieco M. H. Quantitative changes in T helper inducer (CD4+ CD45RA-), T suppressor inducer (CD4+ CD45RA+), T suppressor (CD8+ CD11b+), and T cytotoxic (CD8+ CD11b-) subsets in human immunodeficiency virus infection. J Clin Lab Anal. 1991;5(2):96–100. doi: 10.1002/jcla.1860050205. [DOI] [PubMed] [Google Scholar]
  19. Roederer M., Dubs J. G., Anderson M. T., Raju P. A., Herzenberg L. A., Herzenberg L. A. CD8 naive T cell counts decrease progressively in HIV-infected adults. J Clin Invest. 1995 May;95(5):2061–2066. doi: 10.1172/JCI117892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Smerdon R. A., Peakman M., Hussain M. J., Alviggi L., Watkins P. J., Leslie R. D., Vergani D. Increase in simultaneous coexpression of naive and memory lymphocyte markers at diagnosis of IDDM. Diabetes. 1993 Jan;42(1):127–133. doi: 10.2337/diab.42.1.127. [DOI] [PubMed] [Google Scholar]
  23. Sohen S., Rothstein D. M., Tallman T., Gaudette D., Schlossman S. F., Morimoto C. The functional heterogeneity of CD8+ cells defined by anti-CD45RA (2H4) and anti-CD29 (4B4) antibodies. Cell Immunol. 1990 Jun;128(1):314–328. doi: 10.1016/0008-8749(90)90028-p. [DOI] [PubMed] [Google Scholar]
  24. Teitel J. M., Freedman J. J., Garvey M. B., Kardish M. Two-year evaluation of clinical and laboratory variables of immune function in 117 hemophiliacs seropositive or seronegative for HIV-1. Am J Hematol. 1989 Dec;32(4):262–272. doi: 10.1002/ajh.2830320406. [DOI] [PubMed] [Google Scholar]
  25. de Jong R., Brouwer M., Miedema F., van Lier R. A. Human CD8+ T lymphocytes can be divided into CD45RA+ and CD45RO+ cells with different requirements for activation and differentiation. J Immunol. 1991 Apr 1;146(7):2088–2094. [PubMed] [Google Scholar]

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