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.
Mead
J R
JR
Institute for Antiviral Research, Utah State University, Logan 84322-5600.
Burger
R A
RA
Morrey
J D
JD
Warren
R P
RP
Okleberry
K M
KM
Sidwell
R W
RW
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