Effect of low-dose IL-2 immunotherapy on frequency and phenotype of regulatory T cells and NK cells in HIV/HCV-coinfected patients.
We evaluated the effect of low-dose IL-2 therapy (daily 1.2 MIU/m(2), subcutaneously) on the number and phenotype of regulatory T cells (T(regs)) and natural killer (NK) cells in HIV/HCV-coinfected patients taking antiretroviral therapy. The frequency and phenotype of circulating T(regs) (defined as CD3(+) CD4(+) CD25(high) or CD3(+) CD4(+) FOXP3(+)) and NK cells (CD3(-) CD16(+)/CD56(+)) were evaluated at baseline and after 12 weeks of treatment. The expression of CD25, CTLA-4, and granzymes A and B by CD4(+) FOXP3(+) cells, as well as the expression of KIR receptors (NKB1, CD158a, and NKAT2) on NK cells, was evaluated. Low doses of IL-2 resulted in the augmented frequency and absolute number of T(regs) in coinfected individuals. FOXP3 levels per cell as well as augmented CD25 and CTLA-4 expression by T(regs) suggested that IL-2 may lead to both expansion and activation of T(regs), although changes in the proportion of CD4(+) FOXP3(+) cells were not associated with changes in HCV viral load and CD4(+) cells between baseline and week 12. NK cell frequency also increased after IL-2 therapy. Interestingly, the pattern of expression of KIR receptors was changed by IL-2 treatment, since the frequency of NK cells expressing NKB1 augmented whereas the frequency of NK expressing CD158a and NKAT2 decreased.
Velilla
P A
PA
Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Shata
M T
MT
Lages
C S
CS
Ying
J
J
Fichtenbaum
C J
CJ
Chougnet
C
C
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000628:therapy; D015497:HIV-1; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications / Q000276:immunology / Q000628:therapy; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology*; D016896:Treatment Outcome
D000998:Antiviral Agents; D007376:Interleukin-2; D011092:Polyethylene Glycols; D012254:Ribavirin; D007372:Interferons