Effect of immunomodulators in the hu-PBL-SCID mouse model.
The effects of two immunomodulators were investigated in severe combined immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL-SCID mice). Both immunomodulators, maleic anhydride divinyl ether (MVE-2) and 4-imino-1,3-diazobicyclo-(3.1.0)-hexan-2- one (imexon), have been previously studied by us in retrovirus-infected mice. To determine the effects of these compounds as they may function in humans, 24 SCID mice were each reconstituted with 20 x 10(6) ficoll-purified lymphocytes from a single donor. Five weeks after reconstitution, the mice received 16 mg/kg/day of MVE-2 intraperitoneally (i.p.) on days 0, 7, and 14 or 110 mg/kg/day of imexon i.p. daily for 14 days. Spleens were removed and splenocytes labeled with monoclonal antibodies for T- and B-cell enumeration as determined by flow cytometry 24 h after final treatment. Imexon-treated mice demonstrated a slight increase in total T cells and T cell subsets compared to control mice. T helper/T suppressor cell ratios in imexon-treated mice were brought to a normal 3:2 ratio compared to placebo-treated mice. Human immunoglobulin levels were markedly increased in imexon-treated mice. MVE-2-treated hu-PBL-SCID mice had significantly reduced numbers of total T cells compared to controls. The T-cell population results using human cells in SCID mice were similar to the effects of these immunomodulators on murine cells in immunologically competent mice.
Institute for Antiviral Research, Utah State University, Logan 84322-5600.
J R
JR
Mead
R A
RA
Burger
J D
JD
Morrey
R P
RP
Warren
K M
KM
Okleberry
R W
RW
Sidwell
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002452:Cell Count / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006588:Hexanones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007136:Immunoglobulins / Q000032:analysis*; D007274:Injections, Intraperitoneal; D051379:Mice; D016513:Mice, SCID; D011713:Pyran Copolymer / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D006588:Hexanones; D007136:Immunoglobulins; D011713:Pyran Copolymer; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one