In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major histocompatibility complex gene products.

Boîtard, Christian; Michie, Sara A.; Serrurier, Peter; Butcher, Geoffrey W.; Larkins, A. P.; McDevitt, Hugh O.

doi:10.1073/pnas.82.19.6627

Cited by 79 publications

(23 citation statements)

References 28 publications

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“…In our study, 0X6 enhanced the response of the UPCC.5 cell line. The results of the in vivo experiments of Boitard et al (15) are thus similar to the results of our in vitro studies with islet cell-specific T-lymphocyte lines.…”

Section: Discussionsupporting

confidence: 81%

“…The results of our in vitro experiments with T-lymphocytes specific for ICAg strongly implicate RT1 .D u as the restricting MHC antigen in this rat model of IDDM. Interestingly, the in vivo injection of anti-D u but not anti-B u monoclonal antibodies reduces the incidence of IDDM in BB rats (15). In fact, anti-RT1 .B u antibodies appear to increase the incidence of IDDM.…”

Section: Discussionmentioning

confidence: 99%

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Major Histocompatibility Complex Restriction of T-Lymphocyte Responses to Islet Cell Antigens in IDDM Rats

et al. 1987

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SUMMARY BBUF rats, derived from BB rats, spontaneously develop a form of insulin-dependent diabetes mellitus (IDDM) associated with infiltration of the islets of Langerhans by lymphocytes (insulitis). BBUF rats bear theT he BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM). Genetic studies reveal that the major histocompatibility complex (MHC) restricts the expression of disease in hybrid rats derived by crossing BB rats with non-diabetes-prone rat strains (1). Thus, only rats that are homozygous or heterozygous for RT1 U develop IDDM. Furthermore, only the class II subregions of the RT1 U complex appear to be necessary for disease expression (2). Because no recombinant MHC haplotypes separating the B u and D u class II loci are currently available, genetic studies cannot establish the exact MHC subregion restricting the expression of IDDM in BB rats. We studied the responses of a T-lymphocyte line obtained from the pancreas of a diabetic rat and three T-lymphocyte hybridomas derived from diabetic rats that all respond when stimulated by islet cell antigens (ICAg) and antigen-presenting cells. Antisera and monoclonal antibodies reacting against rat MHC antigens were added to the culture system. Results show that antisera against the entire RT1 U complex inhibited the response of these T-lymphocytes. Moreover, a monoclonal antibody against RT1 .D class II antigens (analogous to HLA-DR in the human and I-E in the mouse) also inhibited proliferation, whereas a monoclonal antibody against RT1.B antigens (analogous to HLA-DQ in the human and I-A in the mouse) had no inhibitory effect. These results suggest that the RT1 .D class II antigens of the rat MHC play a critical role in presenting antigen to autoreactive T-lymphocytes in rat IDDM.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Major Histocompatibility Complex Restriction of T-Lymphocyte Responses to Islet Cell Antigens in IDDM Rats

et al. 1987

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“…(24), and allograft rejection (25)(26)(27). On the basis of these observations, anti-class II mAbs have been used to prevent the development of several autoimmune diseases, including experimental allergic encephalomyelitis (14), experimental myasthenia gravis (15), the spontaneous lupus syndrome of (NZB x NZW)F1 mice (16), type II collagen arthritis in mice (17), and spontaneous IDDM in BB rats (18). The present work extends the previous demonstration with BB rats that anti-class II antibodies protect against autoimmune IDDM to the NOD mouse model.…”

Section: Zg1mentioning

confidence: 99%

“…Autoimmune diseases associated with class II MHC antigens also have been prevented by in vivo administration of anti-class II mAbs (14)(15)(16)(17). Spontaneous IDDM has been prevented in BB rats by an antibody directed against the I-E equivalent of rat class II antigen (18). The prevention of autoimmune diseases by anti-class II mAb treatment has obvious potential therapeutic implications.…”

mentioning

confidence: 99%

Prevention of diabetes in nonobese diabetic mice by anti-I-A monoclonal antibodies: transfer of protection by splenic T cells.

Boîtard

Bendelac

Richard

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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111

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The nonobese diabetic (NOD) mouse has been developed as a model for insulin-dependent diabetes. One gene required for the development of diabetes is associated with the major histocompatibility complex. This gene possibly could be linked to class II genes, which show a unique pattern in NOD mice. To evaluate the role of the I-A class II antigen expressed in NOD mice, we studied the effect of anti-I-A monoclonal antibodies on disease onset in vivo. Long-term treatment with anti-class II IgG2a antibodies specific for NOD I-A antigen prevented the spontaneous development of diabetes, as opposed to control antibodies shown not to react with NOD I-A antigen. Anti-class II antibodies apparently elicited active immune suppression, requiring a fully immunocompetent host, rather than passive blockade of class II antigen. Treatment with anti-class II antibody effectively prevented the adoptive transfer of diabetes produced by splenocytes from diabetic NOD mice into newborn mice but failed to prevent adoptive transfer into irradiated adult NOD recipients. Direct evidence for the induction of suppressor cells was obtained from the passive transfer of spleen cells from anti-class II antibody-treated NOD donors. The injection of anti-class II antibody-treated spleen cells collected from NOD donors prevented the development of diabetes, which normally follows transfer of diabetogenic spleen cells into irradiated 8-week-old male NOD recipients. Depletion experiments indicate that CD41 cells are responsible for anti-class II-induced protection transferred by spleen cells.

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“…Thus, selective inhibition of MHC molecules, which are associated with autoimmunity, by using monoclonal antibodies can delay and ameliorate autoimmune diseases (Kuby, 1994). For example, treatment with anti-MHC class II monoclonal Abs (monoclonal Abs to the murine I-E equivalent) prevented thyroidal and pancreatic autoimmunity in BioBreeding/Worcester (BB/W) rats (Boitard et al, 1985). Treatment of anti-I-A monoclonal Abs ameliorated many autoimmune diseases in animal models including lupus nephritis (NZB/W F1) (Adelman et al, 1983), experimental autoimmune uveoretinitis (Rao et al, 1989), and experimental autoimmune myasthenia gravis (Waldor et al, 1983).…”

Section: Therapies Targeting Mhc Molecules or Antigen-presenting Cellmentioning

confidence: 99%

New Therapeutic Challenges in Autoimmune Diseases

Choi¹

2012

Autoimmune Diseases - Contributing Factors, Specific Cases of Autoimmune Diseases, and Stem Cell and Other Therapies

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In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major histocompatibility complex gene products.

Abstract: Evidence is accumulating that the development of insulin-dependent diabetes mellitus involves autoimmune phenomena, both in the human and in the BB rat model. A strong association is observed in both cases with alleles of the class H major histocompatibility complex (MHC). Results

Cited by 79 publications

References 28 publications

Major Histocompatibility Complex Restriction of T-Lymphocyte Responses to Islet Cell Antigens in IDDM Rats

Major Histocompatibility Complex Restriction of T-Lymphocyte Responses to Islet Cell Antigens in IDDM Rats

Prevention of diabetes in nonobese diabetic mice by anti-I-A monoclonal antibodies: transfer of protection by splenic T cells.

New Therapeutic Challenges in Autoimmune Diseases

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