Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected patients treated with interleukin-2. ANRS 048 IL-2 Study Group.
BACKGROUND
The treatment of HIV-infected patients with interleukin (IL)-2 causes a sustained increase in CD4+ T-lymphocyte counts, involving both naive and memory cells. However, the short-term immunological effects of IL-2, which may shed light on the mechanism of immune reconstitution by this cytokine, are unknown.


OBJECTIVE
To evaluate the acute effect of IL-2 on circulating T-lymphocyte subpopulations and their expression of chemokine receptors.


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-helper (TH) lymphocytes. This was associated with a large increase in CC-chemokine receptor (CCR)-5 and CCR-2b expression by TH cells. Before IL-2 treatment, 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 upregulated in CD62L- memory TH lymphocytes, but also in CD62L+ memory and in naive (CD62L+ CD45RO-) TH lymphocytes. IL-2 treatment also increased the function 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 redistribution.
Zou
W
W
INSERM U131, Institut Paris-Sud sur les Cytokines and Service de Médecine Interne et d'Immunologie Clinique, Hôpital Antoine Béclère, Clamart, France.
Foussat
A
A
Houhou
S
S
Durand-Gasselin
I
I
Dulioust
A
A
Bouchet
L
L
Galanaud
P
P
Levy
Y
Y
Emilie
D
D
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology*
D007376:Interleukin-2; D019713:Receptors, CCR5