Anti-idiotypic antibodies in a patient with a functioning renal graft

Miyajima, T; Higuchi, Reiko; Kashiwabara, Hidefumi; Yokoyama, Takeo; Fujimoto, Shigeyoshi

doi:10.1038/283306a0

Cited by 29 publications

(6 citation statements)

References 14 publications

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“…Only one of the two sera studied in detail in this respect seemed to ful fill this criterion, whereas the other com pletely failed to discriminate. The presence of such anti-idiotypic antibodies in several spe cies including man was found to negatively correlate with the levels of alloantibodies [10,12,17], Such a relation was not observed in our series. In fact, donor-specific alloanti bodies were demonstrated in only 1 patient who, at the same time, had fairly high anti body levels directed against donor-specific TCL, whereas no donor-specific alloantibod ies were detectable in any of the 22 sera from the other 5 patients negative for binding to donor-specific TCL.…”

Section: Discussioncontrasting

confidence: 44%

“…We thought that this possibility was unlikely since im mune complex receptors are known to be expressed on both lectin-and alloantigenactivated T cells [22], whereas the IgG bind ing described here is largely confined to do nor-specific TCL. Secondly, IgG binding to donor-specific T-cells could represent antiidiotypic antibodies induced by T cells acti vated by the graft in vivo as shown in a patient with an allograft [12] or in sera of parous women [17], Several findings seem to exclude this possibility: anti-idiotypic anti bodies directed against alloantigen binding T-cell receptors should be capable of discrim inating between TCL recognizing different HLA specificities. Only one of the two sera studied in detail in this respect seemed to ful fill this criterion, whereas the other com pletely failed to discriminate.…”

Section: Discussionmentioning

confidence: 99%

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Use of Donor-Specific T-Cell Lines for Monitoring of Human Allograft Recipients

et al. 1986

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Donor-specific and highly cytotoxic T-cell lines (TCL) as well as lectin-induced TCL were established from pretransplant lymphocytes of 6 cadaveric renal allograft recipients. These TCL were used in the ¹²⁵I-staphylococcus protein A assay to detect IgG antibodies in pre- and posttransplant sera of these patients preferentially binding to autologous donor-specific TCL. Such antibodies were detected in pretransplant sera from 4 of these 6 allograft recipients. Antibody levels in these 4 patients and in 1 additional case who became positive after transplantation further increased during acute cellular rejection episodes. They disappeared after successful treatment but remained elevated until transplantectomy for treatment of irreversible rejection in 1 case. IgG antibodies binding to autologous lectin-induced TCL were detected in only 1 patient and exhibited a pattern clearly different from those binding to donor-reactive TCL. Although attempts to define the antigenic specificity of the autoantibodies binding to donor-specific TCL by genetical and biochemical means has remained unsuccessful so far, the demonstration of their relationship to in vivo expansion of donor-reactive immune cells deserves further attention.

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Section: Discussioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Use of Donor-Specific T-Cell Lines for Monitoring of Human Allograft Recipients

et al. 1986

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“…This difference in results may be explained by slight differences in the homozygous typing cells as compared to the donor cells. Although the development of donor-specific hyporeactiv ity or tolerance, as determined by in vitro assays, has been noted previously, the precise mechanisms responsible for its induction remain unresolved [2][3][4][5][6][7], Several mecha nisms have been implicated and include the involvement of suppressor cells [7][8][9], antiidiotypic antibodies [10], antiidiotypic T cells [11], veto cells [12] and clonal dele tion [8,13], More recent reports have suggested that the migration of donor leukocytes from organ transplant and the persistence of these cells in recipient tissues may explain allograft acceptance, and is responsible for the development of donor-specific hvporesponsiveness [14,15], It would be interesting to test our patients for donor cell chimerism, to see if it was present in the patients with Sequential MLC after Kidney Transplantation donor-specific hyporesponsiveness and absent in the pa tients with donor-specific sensitization or unchanged do nor-specific T-cell responses.…”

Section: Months Posttransplantationmentioning

confidence: 99%

Sequential Mixed Lymphocyte Culture after Kidney Transplantation: Induction of Tolerance or Sensitization

Creemers

Toit²,

Cassidy³

et al. 1997

Nephron

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Serial mixed lymphocyte culture (MLC) was used to monitor the evolution of donor-specific responsiveness over the first 2 years after cadaveric renal transplantation. Lymphocytes obtained from 37 patients at 0, 1, 3, 6, 12, 18 and 24 months following transplantation were assayed in a one-way MLC using donor lymphocytes as stimulator cells. Donor-specific hyporesponsiveness developed in 66% of the patients with functioning grafts. Donor-specific sensitization was noted in 2 patients with functioning grafts and the MLC reactivity remained unchanged compared to the pretransplant value in 8 patients. The patients with donor-specific hyporeactivity tended to remain either free of rejection episodes or experienced early rejection episodes only. Thus, using serial MLC we were able to identify patients who developed hyporeactivity or tolerance to donor antigens. These patients may require less immunosuppression.

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“…In principle, responder inhibition with restriction to certain stimulator cells can be explained by the presence of idiotype specifix antibody molecules (Binz & Askonas, 1975, Sell et al 1977, Miyajima et al 1980. The observed responder inhibition by our antiserum was, however, more likely to be either the consequence of unexpected cross-reactivity of anti-HLA-B7 molecules with HLA-B8 antigens, or was caused by binding of the Fc piece of the antibody molecules to Fc receptors on responder cells.…”

mentioning

confidence: 62%

Inhibition of responder cell activity in mixed leukocyte culture reactions

et al. 1981

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In a previous report we described a human allo-antiserum which showed MHC restricted dual specific inhibition of mixed leukocyte culture (MLC) reactions (de Rooij et al. 1980). Responder cells were preincubated with the antiserum and washed. Inhibition of MLC reactions occurred if HLA-B8 positive responder cells and HLA-B7 or B40 positive stimulator cells were used. The mechanism of inhibition by this antiserum was investigated and described in this report. The results strongly suggested that the observed inhibition was due to HLA-B7 specific antibody molecules cross-reacting with HLA-B8 antigens. We decided on the following mechanism: HLA-B7 specific antibody molecules bind to HLA-B8 antigens on responder cells at 4 degrees C. Bound antibody molecules area readily released at 37 degrees C and the bind preferentially to HLA-B7 or -B40 positive stimulator cells. Stimulator cells are then lysed by antibody dependent cellular cytotoxicity (ADCC), resulting in impaired MLC reaction. This conclusion was derived from the following observations: 1. HLA-B7 positive cells could be lysed due to antibody molecules bound to B8 positive cells: a. Cells coated with antibody molecules lysed B7 or B40 positive target cells. b. Antibody molecules released from B8 positive cells lysed B7 or B40 positive target cells in ADCC. 2. The active antibody molecules were HLA-B7 specific: a. The inhibiting antibody molecules in the antiserum could be absorbed on and eluted from HLA-B7 positive platelets (de Rooij et al. 1980). b. Antibody molecules bound to and released from HLA-B8 positive cells carried the same B7 specific inhibiting and cytotoxic activity as the original antiserum. 3. The site of recognition on HLA-B8 positive cells is the HLA-B8 antigen: a. F(ab')2 preparations from HLA-B8 and -Bw6 specific antisera inhibited antibody binding to B8 positive cells. b. Antibody binding was not restricted to B, T, FcR+, FcR- or non adherent cell subpopulations. 4. The antibody molecules bind to B8 positive cells with the antigen binding site and not with the Fc part of the molecule: a. Antibody binding could be blocked partially with a F(ab')2 preparation from the original antiserum but not with a Fc preparation. b. The antigen binding site of antibody molecules bound to HLA-B8 positive cells was not freely available, since the MLC inhibiting activity of sensitised B8 positive cells could not be blocked by soluble HLA-B7 antigens. c. The antiserum was cytotoxic for HLA-B8 positive target cells in ADCC. The observed inhibition of MLC by antibody molecules with apparent dual specificity is thus the consequence of a shared or a similar antigenic determinant of HLA-B7 and HLA-B8 antigen molecules.

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Anti-idiotypic antibodies in a patient with a functioning renal graft

Cited by 29 publications

References 14 publications

Use of Donor-Specific T-Cell Lines for Monitoring of Human Allograft Recipients

Use of Donor-Specific T-Cell Lines for Monitoring of Human Allograft Recipients

Sequential Mixed Lymphocyte Culture after Kidney Transplantation: Induction of Tolerance or Sensitization

Inhibition of responder cell activity in mixed leukocyte culture reactions

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