Wp. Zou et al., Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected patients treated with interleukin-2, AIDS, 13(4), 1999, pp. 455-463
Background: The treatment of HIV-infected patients with interleukin (IL)-2
causes a sustained increase in CD4+ T-lymphocyte counts, involving both nai
ve and memory cells. However, the short-term immunological effects of IL-2,
which may shed light on the mechanism of immune reconstitution by this cyt
okine, are unknown.
Objective: To evaluate the acute effect of IL-2 on circulating T-lymphocyte
subpopulations and their expression of chemokine receptors.
Design and methods: Flow cytometry, reverse transcriptase polymerase chain
reaction and chemokine receptor function experiments were performed before
and after 5 days of IL-2 administration in 30 HIV-infected patients.
Results: IL-2 induced an acute lymphopenia of both naive and memory T-helpe
r (TH) lymphocytes. This was associated with a large increase in CC-chemoki
ne receptor (CCR)-5 and CCR-2b expression by TH cells. Before IL-2 treatmen
t, CCR-5 was mostly produced by CD62L- memory TH lymphocytes. After 5 days
of IL-2 administration, the level of CCR-5 mRNA in circulating cells was 18
.6 times higher than before treatment (P < 0.002). CCR-5 expression was upr
egulated in CD62L-memory TH lymphocytes, but also in CD62L+ memory and in n
aive (CD62L+ CD45RO-) TH lymphocytes. IL-2 treatment also increased the fun
ction of CCR-5 in TH cells.
Conclusions: Chemokine receptors are involved in trafficking of lymphocytes
. The IL-2-induced upregulation of chemokine receptors in TH cells may thus
play a role in the acute effects of this cytokine in TH lymphocyte redistr
ibution. (C) 1999 Lippincott Williams & Wilkins.