Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection
AUTOR(ES)
Natarajan, Ven
FONTE
National Academy of Sciences
RESUMO
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 106 naive 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 labeled ex vivo with 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=125022Documentos Relacionados
- O papel das células Treg e da IL-2 na resposta policlonal de células CD4+ durante a infecção pelo Plasmodium chabaudi.
- Differentiation of naive CD4+ T cells towards T helper 2 cells is not impaired in rheumatoid arthritis patients
- Diminished Proliferation of Human Immunodeficiency Virus-Specific CD4+ T Cells Is Associated with Diminished Interleukin-2 (IL-2) Production and Is Recovered by Exogenous IL-2
- Recombinant Interleukin-7 Induces Proliferation of Naive Macaque CD4+ and CD8+ T Cells In Vivo
- Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection