Background: In this study, severe combined immunodeficiency (SCID) mice, which permit the survival of lymphoid cells of human origin, were used to study the human anti-tetanus immune response. Methods: Human peripheral blood lymphocytes (hu-PBL) obtained from 88 healthy donors (aged from 18 to 62) were transplanted into SCID mice, and anti-tetanus toxoid (Ttd) antibody production and protection against lethal doses of tetanus toxin (Ttx) were investigated in the hu-PBL-SCID mice. Results: The transfer of human PBL evoked significant human anti-Ttd IgG antibody production for 37.5% of the donors. After in vivo immunization, the percentage of donors with PBL exhibiting positive anti-TtD IgG production in the mice increased to 54.5%. Mean anti-Ttd IgG levels in the sera were also significantly elevated in response to immunization. The mean IgG titer for the mice injected with PBL from donors under the age of 40 was significantly higher than that of the mice injected with PBL from donors aged 40 or older. Four weeks after the cell transfer, the mice were challenged with Ttx. The induction of protection against Ttx challenge was observed mostly in mice with PBL transferred from donors under the age of 40. In vivo immunization in SCID mice with Ttd increased the number of cases of resistance to Ttx. Conclusions: These results suggest that hu-PBL-SCID mice might serve as a tool for predicting the protective ability against pathogens in PBL donors and also for evaluating vaccine efficacy.

Keywords:
hu-PBL-SCID, Tetanus, Protection, Vaccine, Evaluation
1.
Bosma GC, Custer RP, Bosma MJ: A severe combined immunodeficiency mutation in the mouse. Nature 1983;301:527–530.
2.
Mosier DE, Gulizia RJ, Baird SM, Wilson DB: Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 1988;335:256–259.
3.
Bonyhadi ML, Kaneshima H: The SCID-hu mouse: An in vivo model for HIV-1 infection in humans. Mol Med Today 1997;3:246–253.
4.
Carlsson R, Martensson C, Kalliomaki S, Ohlin M, Borrebaeck CAK: Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies. J Immunol 1992;148:1065–1071.
5.
Ifversen P, Borrebaeck CAK: SCID-hu-PBL: A model for making human antibodies? Semin Immunol 1996;8:243–248.
6.
Jackson DJ, Kumpel BM: Optimisation of human anti-tetanus toxoid antibody responses and location of human cells in SCID mice transplanted with human peripheral blood leukocytes. Hum Antibodies 1997;8:181–188.
7.
Roncarolo MG, Carballido JM, Rouleau M, Namikawa R, de Vries JE: Human T- and B-cell functions in SCID-hu mice. Semin Immunol 1996;8:207–213.
8.
Mazingue C, Cottrez F, Auriault C, Cesbron J-Y, Capron A: Obtention of a human primary humoral response against schistosome protective antigens in severe combined immunodeficiency mice after the transfer of human peripheral blood mononuclear cells. Eur J Immunol 1991;21:1763–1766.
9.
Aaberge IS, Michaelsen TE, Rolstad AK, Groeng E-C, Solberg P, Lovik M: SCID-hu mice immunized with a pneumococcal vaccine produce specific human antibodies and show increased resistance to infection. Infect Immun 1992;60:4146–4153.
10.
Sato H, Takahashi M: Tetanus vaccine; in Researcher’s Associates, The National Institute of Health (ed): Vaccine Handbook. Tokyo, Maruzen, 1996, pp 60–67.
11.
Steinsvik TE, Aaberge IS, Gaarder PI, Bjonness U, Lovik M: Total and birch pollen-specific human IgE in mice with severe combined immunodeficiency transplanted with human peripheral blood lymphocytes: Donor dependence, seasonal variation and in vivo half-life. Int Arch Allergy Immunol 1997;112:175–183.
12.
Pollock PL, Germole DR, Comment CE, Rosenthal GL, Luster MI: Development of human lymphocyte-engrafted SCID mice as a model for immunotoxicity assessment. Fundam Appl Toxicol 1994;22:130–138.
13.
Ahnert-Hilger G, Dauzenroth ME, Habermann E, Henschen A, Kriegstein K, Mauler F, Weller U: Chains and fragments of tetanus toxin, and their contribution to toxicity. J Physiol (Paris) 1990;84:229–236.
© 2000 S. Karger AG, Basel
2000
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