Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection
| Autor: | Julia A. Metcalf, Randy Stevens, Joseph A. Kovacs, Joseph W. Adelsberger, Irini Sereti, Richard A. Lempicki, DaRue Prieto, H. Clifford Lane, Ven Natarajan, Michael Baseler, Yunden Badralmaa |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Interleukin 2
Adult CD4-Positive T-Lymphocytes Cell division T cell HIV Infections Biology Gene Rearrangement T-Lymphocyte Cohort Studies In vivo medicine Humans Multidisciplinary T-cell receptor Gene rearrangement Telomere Biological Sciences CD4 Lymphocyte Count medicine.anatomical_structure Treatment Outcome Immunology Leukocytes Mononuclear Interleukin-2 Ex vivo Cell Division medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 99(16) |
| ISSN: | 0027-8424 |
| Popis: | Intermittent interleukin-2 (IL-2) therapy has been shown to increase the number of CD4+ T cells, preferentially cells with a naive phenotype, in patients with HIV infection. For this report we investigated the mechanism underlying this expansion by studying the relative roles of peripheral expansion and thymic output. In a cohort of six patients receiving IL-2 over a period of 1 year, the mean number of naive CD4+ T cells increased from 139 to 387 cells per μl while levels of T cell receptor rearrangement excision circles (TRECs) declined from 47,946 to 26,510 copies per 106naive T cells, thus making it unlikely that the CD4+ T cell count increases were secondary to increase in thymic output. To examine directly the impact of IL-2 on peripheral expansion, peripheral blood mature, naive CD4+ T cells were labeledex vivowith 5-bromodeoxyuridine as well as stained directly for Ki67. These studies revealed a 7-fold increase in the percentage of 5-bromodeoxyuridine-positive cells and a 20–40-fold increase in Ki67 staining in the naive CD4+ T cell pool in the setting of IL-2 administration. This degree of increase in mature CD4+ T cell turnover induced by IL-2 does not compromise the future replicative potential of these cells, because longitudinal measurements of telomere length went from 6,981 to 7,153 bp after 1 year of IL-2 therapy. These data strongly suggest that much of the increase in CD4+ cells associated with IL-2 treatment is caused by peripheral expansion of existing naive CD4+ T cells rather than increased thymic output and that these increases occur without compromising the potential of these cells for further cell division. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|