To study the effect of expression of a single foreign antigen on the outcome of otherwise compatible mouse islet grafts, we have used transgenic mice expressing the human complement receptor 2 (CR2, CD21, C3d/EBV receptor) on their pancreatic (β-cells (RIPCR2 mice). Donors were RIP-CR2 mice, typed at the major histocompatibility complex (MHC) as H-2k, H-2b, or H-2bxk, and recipients were streptozotocintreated nontransgenic B6 × CBA Fl mice (H-2bxk). H-2b or H-2bxk CR2-expressing islets were not rejected (mean survival time [MST] >100 days) but induced a peri-insulitis and an antibody response to CR2. In contrast, H-2k CR2-expressing islets were rejected in 80% of the cases with a MST of 65 ± 23 days and were massively infiltrated by a destructive insulitis. In both cases, the infiltrate was mainly made of CD4+ cells, with few CD8+ cells. The isotype of IgG antibody response to CR2 was studied: recipients of H-2k grafts had a predominantly IgGl response, while recipients of H-2b grafts had a balanced IgG2a and IgGl response. To further evaluate the mechanism of differential rejection of the two types of grafts, recipients were immunized with CR2-expressing rat insulinoma cells before transplantation. Preimmunization with CR2 did not affect the outcome of H-2b grafts but greatly accelerated the rejection of H-2k grafts. These experiments indicate that expression of a single foreign antigen on β-cells triggers an immune response leading to rejection or to peri-insulitis, depending on the MHC of donor islets.
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Original Articles|
May 01 1997
Rejection of Islets Differing by a Single Antigen Is Dependent on Donor MHC Free
Murielle Vigneau-Hermellin;
Murielle Vigneau-Hermellin
INSERM U342, Hôpital Saint Vincent de Paul
Paris, France
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Letizia Vitali;
Letizia Vitali
Department of Pediatrics, University of Pavia
Italy
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Isabelle Tardivel;
Isabelle Tardivel
INSERM U342, Hôpital Saint Vincent de Paul
Paris, France
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Myriam Rabaud;
Myriam Rabaud
INSERM U342, Hôpital Saint Vincent de Paul
Paris, France
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Michael V Holers;
Michael V Holers
Department of Medicine (M.V.H.), University of Colorado Health Sciences Center
Denver, Colorado
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Jean-Claude Carel
Jean-Claude Carel
INSERM U342, Hôpital Saint Vincent de Paul
Paris, France
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Address correspondence and reprint requests to Dr. Jean-Claude Carel, INSERM U342, Hôpital Saint Vincent de Paul, 82 av Denfert Rochereau, 75014 Paris, France. [email protected].
1
BG, blood glucose; CTL, cytotoxic T-lymphocyte; OD, optical density; ELISA, enzyme-linked immunosorbent assay; MHC, major histocompatibility complex; RIN, rat insulinoma.
Diabetes 1997;46(5):765–769
Article history
Received:
July 09 1996
Revision Received:
December 12 1996
Accepted:
December 12 1996
PubMed:
9133542
Citation
Murielle Vigneau-Hermellin, Letizia Vitali, Isabelle Tardivel, Myriam Rabaud, Michael V Holers, Jean-Claude Carel; Rejection of Islets Differing by a Single Antigen Is Dependent on Donor MHC. Diabetes 1 May 1997; 46 (5): 765–769. https://doi.org/10.2337/diab.46.5.765
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