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Production of human alloreactive antibodies by uremic sensitized lymphocytes engrafted in severe combined immunodeficient mice.
Production of human alloreactive antibodies by uremic sensitized lymphocytes engrafted in severe combined immunodeficient mice.
- Source :
-
Transplantation [Transplantation] 1999 Oct 27; Vol. 68 (8), pp. 1188-94. - Publication Year :
- 1999
-
Abstract
- Background: Numerous studies have documented antibody responses to nominal antigens in human peripheral blood lymphocyte (hu-PBL)-severe combined immunodeficient (SCID) mice engrafted with PBL. We suggest, therefore, that engraftment of SCID mice by allosensitized cells produces alloreactive antibodies (allo-Ab). As such, SCID mice can be used as a model to examine the cellular basis of the sustenance of humoral alloresponses.<br />Methods: C.B-17 SCID mice were engrafted intraperitoneally with PBL from sensitized uremic patients for 5 weeks and classified into the following: group 1, 8 mice engrafted with unactivated cells (n = 5; n = sensitized patients); group 2, 6 mice engrafted with unactivated PBL (n = 3) followed 2 days later by in vivo activation with interleukin-2 (IL-2) and lipopolysaccharide (LPS); group 3, 11 mice engrafted with cells preactivated in vitro with IL-2 and LPS (n = 6); group 4, 9 mice engrafted with cells preactivated with irradiated allogeneic transformed B cells, IL-2, and LPS (n = 5); group 5, 10 mice engrafted with cells preactivated with IL-2, LPS, and HLA class II allopeptides and adjuvant (n = 6); group 6, 8 control mice engrafted with control cells preactivated with IL-2 and LPS. Two weeks later, each group was rechallenged by the same stimuli. Allo-Ab production was measured by the panel-reactive antibody PRA-STAT ELISA method. Results. Allo-Ab was produced in 54.5% of group 3, 43% of group 4; 80% of group 5, and 0% of groups 1, 2, and 6. The ratio of alloreactive positive wells in the allo-Ab-producing PBL-hu-SCID mice to that present in the respective patient's sera was 82%, 52%, and 87% in groups 3, 4, and 5, respectively. Conclusions. The study demonstrates the feasibility of using the hu-PBL-SCID model to study alloreactive memory B-cell function in humans. Discrete HLA-class allopeptides (group 5) appeared more potent allo-Ab producers than allogeneic cells (group 4).
- Subjects :
- Adjuvants, Immunologic pharmacology
Adult
Animals
B-Lymphocytes immunology
B-Lymphocytes radiation effects
Female
Histocompatibility Antigens Class II pharmacology
Humans
Interleukin-2 pharmacology
Lipopolysaccharides pharmacology
Lymphocyte Activation physiology
Lymphocytes drug effects
Male
Mice
Isoantibodies biosynthesis
Lymphocyte Transfusion
Lymphocytes immunology
Mice, SCID immunology
Uremia immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 68
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 10551649
- Full Text :
- https://doi.org/10.1097/00007890-199910270-00020