Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes

Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-defi...

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Veröffentlicht in:Infection and Immunity 1995-08, Vol.63 (8), p.2867-2872
Hauptverfasser: Molrine, D.C. (Dana-Farber Center Institute, Boston, MA.), Polk, D.B, Ciamarra, A, Phillips, N, Ambrosino, D.M
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container_issue 8
container_start_page 2867
container_title Infection and Immunity
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creator Molrine, D.C. (Dana-Farber Center Institute, Boston, MA.)
Polk, D.B
Ciamarra, A
Phillips, N
Ambrosino, D.M
description Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPRL model
doi_str_mv 10.1128/IAI.63.8.2867-2872.1995
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(Dana-Farber Center Institute, Boston, MA.) ; Polk, D.B ; Ciamarra, A ; Phillips, N ; Ambrosino, D.M</creator><creatorcontrib>Molrine, D.C. (Dana-Farber Center Institute, Boston, MA.) ; Polk, D.B ; Ciamarra, A ; Phillips, N ; Ambrosino, D.M</creatorcontrib><description>Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. 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(Dana-Farber Center Institute, Boston, MA.)</creatorcontrib><creatorcontrib>Polk, D.B</creatorcontrib><creatorcontrib>Ciamarra, A</creatorcontrib><creatorcontrib>Phillips, N</creatorcontrib><creatorcontrib>Ambrosino, D.M</creatorcontrib><title>Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes</title><title>Infection and Immunity</title><addtitle>Infect Immun</addtitle><description>Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. 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Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPRL model</abstract><cop>Washington, DC</cop><pub>American Society for Microbiology</pub><pmid>7622207</pmid><doi>10.1128/IAI.63.8.2867-2872.1995</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Antibodies, Bacterial - biosynthesis
Antibody Formation
Bacterial diseases
Biological and medical sciences
CARENCE EN VITAMINE
Clostridium tetani
COMPLEMENT ALIMENTAIRE
DEFICIENCIA DE VITAMINAS
Experimental bacterial diseases and models
Humans
IMMUNISATION
Immunoglobulin G - metabolism
IMMUNOGLOBULINE
Infectious diseases
INMUNIZACION
INMUNOGLOBULINA
LINFOCITOS
LYMPHOCYTE
Lymphocytes - immunology
Medical sciences
Mice
Mice, SCID - immunology
MODELE ANIMAL
MODELOS ANIMALES
RATON
REPONSE IMMUNITAIRE
RESPUESTA INMUNOLOGICA
RETINOL
SOURIS
SUPLEMENTOS
Tetanus Toxoid - immunology
Vitamin A Deficiency - immunology
VITAMINAS
VITAMINE
title Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes
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