An IL-2/Ig fusion protein influences CD4+ T lymphocytes in naive and simian immunodeficiency virus-infected Rhesus monkeys.
The T cell-stimulatory cytokine interleukin 2 (IL-2) is being evaluated as a therapeutic in the clinical settings of HIV infection and cancer. However, the clinical utility of IL-2 may be mitigated by its short in vivo half-life, toxic effects, and high production costs. We show here that an IL-2/Ig fusion protein possesses IL-2 immunostimulatory activity in vitro and a long in vivo half-life. IL-2/Ig treatment of healthy rhesus monkeys induced significant increases in CD4(+) T lymphocyte counts and expression of CD25 by these cells. Short courses of IL-2/Ig treatment of simian immunodeficiency virus (SIV)-infected rhesus monkeys in conjunction with antiretroviral drugs resulted in increased CD25 expression on T lymphocytes, and transient increases in CD4(+) T lymphocyte counts. Plasma viremia did not increase in these treated animals. Treatment of healthy or SIV-infected rhesus monkeys with a plasmid encoding the IL-2/Ig protein did not affect CD4(+) T lymphocytes. These results demonstrate that IL-2/Ig has potential utility as an immunostimulatory therapeutic.
Craiu
A
A
Science Research Laboratory, Somerville, Massachusetts 02115, USA.
Barouch
D H
DH
Zheng
X X
XX
Kuroda
M J
MJ
Schmitz
J E
JE
Lifton
M A
MA
Steenbeke
T D
TD
Nickerson
C E
CE
Beaudry
K
K
Frost
J D
JD
Reimann
K A
KA
Strom
T B
TB
Letvin
N L
NL
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000235:genetics / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008253:Macaca mulatta; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D014162:Transfection; D019562:Viral Load
D019380:Anti-HIV Agents; D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins