BACKGROUND: Intermittent interleukin (IL)-2 administration to human immunodeficiency virus (HIV)-infected patients leads to CD4(+) T cell expansions. The factors potentially affecting these expansions were investigated in the present study. METHODS: A matched (for baseline CD4(+) T cell count) case-control study was designed. Nonresponders (NRs) were defined as patients with a <or=10% increase in CD4(+) T cell count 2 months after the third IL-2 cycle (week 24), compared with that at baseline (week 0). Control subjects experienced a >or=50% increase in CD4(+) T cell count at week 24. Immunophenotype, Ki67 and forkhead box protein P3 (FoxP3) expression, and T cell receptor excision circle (TREC) measurements in T cells were evaluated at weeks 0 and 24 in both groups. RESULTS: Control subjects and NRs did not differ significantly at baseline in age, viral load, CD4(+) T cell count, nadir CD4(+) T cell count, or CD8(+) T cell count. At week 0, NRs had lower TREC levels per 1x106 T cells and higher levels of T cell proliferation and activation than did control subjects. At week 24, both groups experienced decreases in T cell proliferation and increases in CD25 and FoxP3 expression on CD4(+) T cells, with TREC levels per 1x106 CD4(+) T cells decreasing significantly only in control subjects. CONCLUSIONS: Increased immune activation can adversely affect CD4(+) T cell expansions after IL-2 administration. Despite the lack of expansion, other evidence of IL-2-induced biological activity was observed.
BACKGROUND: Intermittent interleukin (IL)-2 administration to human immunodeficiency virus (HIV)-infectedpatients leads to CD4(+) T cell expansions. The factors potentially affecting these expansions were investigated in the present study. METHODS: A matched (for baseline CD4(+) T cell count) case-control study was designed. Nonresponders (NRs) were defined as patients with a <or=10% increase in CD4(+) T cell count 2 months after the third IL-2 cycle (week 24), compared with that at baseline (week 0). Control subjects experienced a >or=50% increase in CD4(+) T cell count at week 24. Immunophenotype, Ki67 and forkhead box protein P3 (FoxP3) expression, and T cell receptor excision circle (TREC) measurements in T cells were evaluated at weeks 0 and 24 in both groups. RESULTS: Control subjects and NRs did not differ significantly at baseline in age, viral load, CD4(+) T cell count, nadir CD4(+) T cell count, or CD8(+) T cell count. At week 0, NRs had lower TREC levels per 1x106 T cells and higher levels of T cell proliferation and activation than did control subjects. At week 24, both groups experienced decreases in T cell proliferation and increases in CD25 and FoxP3 expression on CD4(+) T cells, with TREC levels per 1x106 CD4(+) T cells decreasing significantly only in control subjects. CONCLUSIONS: Increased immune activation can adversely affect CD4(+) T cell expansions after IL-2 administration. Despite the lack of expansion, other evidence of IL-2-induced biological activity was observed.
Authors: Sarah W Read; Richard A Lempicki; Michele Di Mascio; Sharat Srinivasula; Rosanne Burke; William Sachau; Marjorie Bosche; Joseph W Adelsberger; Irini Sereti; Richard T Davey; Jorge A Tavel; Chiung-Yu Huang; Haleem J Issaq; Stephen D Fox; H Clifford Lane; Joseph A Kovacs Journal: J Infect Dis Date: 2008-09-15 Impact factor: 5.226
Authors: D Abrams; Y Lévy; M H Losso; A Babiker; G Collins; D A Cooper; J Darbyshire; S Emery; L Fox; F Gordin; H C Lane; J D Lundgren; R Mitsuyasu; J D Neaton; A Phillips; J P Routy; G Tambussi; D Wentworth Journal: N Engl J Med Date: 2009-10-15 Impact factor: 91.245
Authors: Lishomwa C Ndhlovu; Elizabeth Sinclair; Lorrie Epling; Qi Xuan Tan; Terence Ho; Aashish R Jha; Ijeoma Eccles-James; Camilla Tincati; Jay A Levy; Douglas F Nixon; Frederick M Hecht; Jason D Barbour Journal: J Clin Immunol Date: 2010-06-23 Impact factor: 8.317