Acute activation of CD8+ T lymphocytes in interleukin-2-treated HIV-infected patients. ANRS-048 IL-2 Study Group. Agence Nationale de Recherches sur le SIDA.
CD8+ T lymphocytes play a key role in the control of HIV infection, through both cytotoxic and noncytotoxic mechanisms. To study in vivo effects of interleukin-2 (IL-2) treatment on this cell compartment, the level of activation of CD8+ T lymphocytes was evaluated before and just after 5-day administration of IL-2 in 16 HIV-infected patients. The serum level of soluble CD25 and of soluble CD8 significantly increased following IL-2 administration. The number of mRNA molecules coding for perforin and granzyme B, two enzymes that are contained in granules of cytotoxic cells, also significantly increased in peripheral blood mononuclear cells and in purified CD8+ cells (p < .001). Variations of plasma HIV viremia and perforin gene expression following IL-2 administration were inversely correlated (p = .023), suggesting that IL-2-induced activation of CD8+ T lymphocytes contributes to limit HIV replication in vivo. In contrast to perforin and granzyme B gene expression, IL-2 administration did not increase the expression of macrophage inhibitory protein-1alpha (MIP-1alpha), MIP-1beta, and regulated-on-activation normal T-expressed and secreted (RANTES) genes. These findings indicate that CD8+ T lymphocytes in HIV-infected patients are acutely activated by IL-2 treatment, which may improve long-term control of HIV infection.
Zou
W
W
INSERM U131 and Service de Médecine Interne et d'Immunologie Clinique, Institut Paris-Sud sur les Cytokines, Hôpital Antoine Béclère, Clamart, France.
Foussat
A
A
Capitant
C
C
Durand-Gasselin
I
I
Bouchet
L
L
Galanaud
P
P
Levy
Y
Y
Emilie
D
D
D016827:CD8 Antigens / Q000097:blood; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D053804:Granzymes; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2 / Q000097:blood; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation; D019562:Viral Load
D016827:CD8 Antigens; D018925:Chemokines; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D015375:Receptors, Interleukin-2; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases