T Cells and Natural Killer Cells Regulate Human IgG Subclass Concentrations in SCID Mice

Ambrosino, Donna M.; Wang, Michael; Ciamarra, Angela; Chan, Melvin; Bolon, David L.; Minn, Juno; Jacobsohn, David A.; Finberg, Robert W.

doi:10.1006/cimm.1994.1107

Cited by 9 publications

(3 citation statements)

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“…Much of the decline in the response to these antigens may, in fact, relate to the decreased function of T cells (reviewed in Miller [57]), macrophages [58], splenic NK cells [59,60], and dendritic cells [3] with aging. Ambrosino et al [61] suggest that the production of IgG2 antibodies by human B cells is relatively T cell-independent based on their experiments with highly purified cell populations in severe combined immunodeficient mice, whereas production of IgG1 antibodies relies upon cytokine signals from T cells and accessory cells [62]. The lower levels of anti-MCPS in the elderly subjects at 6 weeks and the more rapid decline in levels by 12 weeks may be due to innate B cell defects with age or a decline in cytokine support for clonal expansion.…”

Section: Discussionmentioning

confidence: 99%

Elderly Immune Response to a TI‐2 Antigen: Heavy and Light Chain Use and Bactericidal Activity toNeisseria meningitidisSerogroup C Polysaccharide

1999

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Previous studies of the elderly immune response to TI-2 antigens failed to correlate specific antibody levels with function and to compare responses with those of young adults. Neisseria meningitidis serogroup C capsular polysaccharide (MCPS) was used as a model TI-2 antigen. Anti-MCPS antibody levels were determined in elderly individuals and correlated with bactericidal activity. The anti-MCPS response in most persons was characterized by predominant IgG usage, with IgG2>IgG1. No light chain or IgA subclass predominated, but some responses showed a particular chain type. Bactericidal activity correlated best with IgG2 levels. Elderly subjects had lower anti-MCPS responses than the young adults did in all chain-specific anti-MCPS levels, and levels declined more rapidly. Bactericidal activity following immunization was significantly lower in the elderly persons. These results suggest the anti-MCPS antibody repertoire in the elderly is likely maintained, and the lower level of function is related to the lower antibody levels.

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Section: Discussionmentioning

confidence: 99%

Elderly Immune Response to a TI‐2 Antigen: Heavy and Light Chain Use and Bactericidal Activity toNeisseria meningitidisSerogroup C Polysaccharide

1999

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“…The combination of a good cellular survival with the early introduction of the appropriate Ag stimulus therefore explains the high concentrations of Ag-specific Ig observed in the TM-g 1pretreated animals. Although a role for the murine APC cannot entirely be excluded [23], it has been shown that the generation of a specific secondary immune response in Hu-PBL-SCID models depends on the presence of human CD4 + Th cells in the graft since xenotransplantation of purified human B cells into these mice did not induce human Ig production [36][37][38]. The stimulation of the human B cells by the T cells is therefore required for the production of human Ig [36].…”

Section: Discussionmentioning

confidence: 99%

Murine IL-2 receptor beta chain blockade improves human leukocyte engraftment in SCID mice

et al. 1998

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Severe combined immunodeficient (SCID) mice accept human xenografts and can act as a model for human immune functions. Murine natural killer cells (NK), however, represent an important barrier for the reconstitution of SCID mice with human peripheral blood leukocytes (Hu‐PBL). We investigated the effect on Hu‐PBL survival of pretreatment with TM‐β1, a rat monoclonal antibody for the mouse IL‐2 receptor beta chain. TM‐β1 greatly improved the survival of Hu‐PBL. Human lymphocytes, predominantly T cells, survived in the peritoneum and infiltrated spleen and lungs already 1 week after engraftment and liver and thymus from 2 weeks on. Secondary humoral responses were evaluated with Hu‐PBL from a donor immune to hepatitis‐B surface Ag (HBsAg) and tetanus toxoid (TT). TM‐β1 pretreatment enhanced the recall Ig response to HBsAg and did not affect the baseline anti‐TT Ig production. In conclusion, TM‐β1 pretreatment of SCID mice significantly improves the survival and functionality of the Hu‐PBL graft.

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“…SCID mice have recently been successfully reconstituted with either human peripheral blood lymphocytes (SCID-huPBL) or fetal tissues (27,28). Human reconstituted SCID mice produce substantial amounts of human immunoglobulin and have been utilized as models of human infection (human immunodeficiency and Epstein-Barr viruses), immune mediate diseases, and immune regulation (3,5,15,25,29,31). We now report on the establishment of a vitamin A-deficient SCID-huPBL model and demonstrate impaired human antibody responses to tetanus toxoid immunization.…”

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confidence: 99%

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

et al. 1995

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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-huPBL model.

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T Cells and Natural Killer Cells Regulate Human IgG Subclass Concentrations in SCID Mice

Cited by 9 publications

References 0 publications

Elderly Immune Response to a TI‐2 Antigen: Heavy and Light Chain Use and Bactericidal Activity toNeisseria meningitidisSerogroup C Polysaccharide

Elderly Immune Response to a TI‐2 Antigen: Heavy and Light Chain Use and Bactericidal Activity toNeisseria meningitidisSerogroup C Polysaccharide

Murine IL-2 receptor beta chain blockade improves human leukocyte engraftment in SCID mice

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

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