Increased peripheral expansion of naive CD4+ T cells in vivo after IL-2 treatment of patients with HIV infection.
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 microl while levels of T cell receptor rearrangement excision circles (TRECs) declined from 47,946 to 26,510 copies per 10(6) 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.
Natarajan
Ven
V
Science Applications International Corporation-Frederick, Inc., Frederick, MD 21702, USA.
Lempicki
Richard A
RA
Sereti
Irini
I
Badralmaa
Yunden
Y
Adelsberger
Joseph W
JW
Metcalf
Julia A
JA
Prieto
Darue A
DA
Stevens
Randy
R
Baseler
Michael W
MW
Kovacs
Joseph A
JA
Lane
H Clifford
HC
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D015331:Cohort Studies; D015329:Gene Rearrangement, T-Lymphocyte / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D016615:Telomere / Q000187:drug effects; D016896:Treatment Outcome
D007376:Interleukin-2