CD4+ T cell responses to interleukin-2 administration in HIV-infected patients are directly related to the baseline level of immune activation.
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.
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. isereti@niaid.nih.gov
Irini
I
Sereti
Peter
P
Sklar
Meena S
MS
Ramchandani
Sarah W
SW
Read
Vinay
V
Aggarwal
Hiromi
H
Imamichi
Ven
V
Natarajan
Julia A
JA
Metcalf
Joseph A
JA
Kovacs
Jorge
J
Tavel
Richard T
RT
Davey
Rebecca
R
Dersimonian
H Clifford
HC
Lane
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology* / Q000627:therapeutic use*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019562:Viral Load
D044966:Anti-Retroviral Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit