Human <i>in vivo</i> antigenic modulation induced by the anti‐T cell OKT3 monoclonal antibody

Chatenoud, Lucienne; Baudrihaye, M.; Kreis, Henri; Goldstein, Gideon; Schindler, John; Bach, Jean‐François

doi:10.1002/eji.1830121116

Cited by 193 publications

(77 citation statements)

References 24 publications

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“…Consistent with this postulate, Schroff et al (21) recognized that antigenic modulation occurred to a far lower degree in vitro than in vivo, and suggested that macrophages in the liver and lungs were responsible for the higher level of in vivo antigenic modulation. Several other investigators have reported similar evidence for antigenic modulation in other systems (2,20,80,82,83). However, to our knowledge, no one has investigated mechanisms based on Fc␥R-mediated transfer of mAbs and targeted Ags from tumor cells to acceptor monocytes/macrophages.…”

Section: Shaving As a Mechanism For Antigenic Modulation: Historical supporting

confidence: 59%

“…The mechanism of shaving, which may underlie many cases of antigenic modulation, includes transfer of mAb and tumor cell Ag to the acceptor monocyte/macrophage, rather than internalization of Ag by the target cell. In certain cases, such internalization (in the absence of monocytes) has clearly been documented (81), but often the reaction requires or is enhanced by accessory cells expressing Fc␥RI (21,22,80,82,83). In fact, our observations bear striking similarities to the reports of Schroff et al (21, 22), who studied antigenic modulation induced by mAb T101 on a lymphocyte membrane-associated Ag (T65), now recognized as CD5 (84).…”

Section: Shaving As a Mechanism For Antigenic Modulation: Historical mentioning

confidence: 99%

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The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes

Beum

Kennedy

Williams

et al. 2006

The Journal of Immunology

209

226

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Clinical investigations have revealed that infusion of immunotherapeutic mAbs directed to normal or tumor cells can lead to loss of targeted epitopes, a phenomenon called antigenic modulation. Recently, we reported that rituximab treatment of chronic lymphocytic leukemia patients induced substantial loss of CD20 on B cells found in the circulation after rituximab infusion, when rituximab plasma concentrations were high. Such antigenic modulation can severely compromise therapeutic efficacy, and we postulated that B cells had been stripped (shaved) of the rituximab/CD20 complex by monocytes or macrophages in a reaction mediated by FcγR. We developed an in vitro model to replicate this in vivo shaving process, based on reacting rituximab-opsonized CD20+ cells with acceptor THP-1 monocytes. After 45 min at 37°C, rituximab and CD20 are removed from opsonized cells, and both are demonstrable on acceptor THP-1 cells. The reaction occurs equally well in the presence and absence of normal human serum, and monocytes isolated from peripheral blood also promote shaving of CD20 from rituximab-opsonized cells. Tests with inhibitors and use of F(ab′)2 of rituximab indicate transfer of rituximab/CD20 complexes to THP-1 cells is mediated by FcγR. Antigenic modulation described in previous reports may have been mediated by such shaving, and our findings may have profound implications for the use of mAbs in the immunotherapy of cancer.

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Section: Shaving As a Mechanism For Antigenic Modulation: Historical supporting

confidence: 59%

Section: Shaving As a Mechanism For Antigenic Modulation: Historical mentioning

confidence: 99%

The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes

Beum

Kennedy

Williams

et al. 2006

The Journal of Immunology

209

226

View full text Add to dashboard Cite

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“…Gray et a1 have reported that lymphocytopenia is corrected within 1-2 weeks following therapy (19). In OKT3-treated patients, peripheral cell numbers have been shown to increase 2-5 days after termination of antibody infusion (20). i n our 2 patients, reduction of peripheral T cell numbers persisted for up to 2 months, although no further immunosuppressive therapy was used.…”

Section: Discussionmentioning

confidence: 52%

Long‐term immunomodulatory effects of t lymphocyte depletion in patients with systemic sclerosis

Goronzy

Weyand

1990

Arthritis & Rheumatism

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We describe 2 patients with rapidly progressing systemic sclerosis that did not respond to conventional therapy, who were treated with a 5-day regimen of T cell-specific antilymphocyte globulin. One patient had deteriorating pulmonary involvement, and the second patient had developed disabling skin disease with multiple ulcers and gangrene. Both patients showed improvement concomitant with almost complete elimination of CD4+ and CDS+ T lymphocytes. Regeneration of peripheral T cells required 60-90 days and was followed by a long-term inversion of the CD4:CDS ratio. The persistent therapeutic effect in both patients correlated with the lack of CD4+ T cells and the predominance of CDS+ T cells. This suggests a crucial role of T cell immunity in the pathogenesis of systemic sclerosis. In vitro studies of regenerating T cells demonstrated that CD4+ helperhnducer cells were functionally competent. Alterations in the composition of the CDS+ population may explain the prolonged suppression of CD4+ T cells observed during the period of therapeutic benefit. Systemic sclerosis (SSc; scleroderma) is a poorly understood disease for which there are few effective treatments. It is characterized by progressive inflammation and fibrosis of the skin, that leads to hidebound From the Division of Rheumatology, Department of Medicine V, University of Heidelberg, Heidelberg, Federal Republic of fibrotic skin adherent to joints and tendons, and epidermal atrophy. The rate of progression is unpredictable, and the outcome of the disease is determined by the involvement of crucial viscera, such as the lungs, kidneys, and gastrointestinal tract.The pathogenesis of SSc has not been resolved. T cell infiltration in early sclerodermatous lesions has been reported, which supports the idea of an immunologically mediated disease (1,2). However, it is not clear how the characteristic proliferative vascular lesions and obliterative vascular changes, which are interpreted as a consequence of repeated episodes of endothelial cell injury, are related to the frequent autoimmune phenomena in SSc patients (3). The recent finding that collagen synthesis is under the control of various lymphokines, most of which are secreted by activated T cells, may represent a missing link between immunologic response and vascular damage (4-6). Although conventional immunosuppressive therapy has failed to improve the outcome of SSc, the modulation of T cell responses and lymphokine secretion may lead to the development of new therapeutic procedures.We have recently observed the rapid progression of systemic sclerosis in 2 patients, which necessitated the use of aggressive therapeutic regimens. The first patient presented with progressive lung disease that was not responsive to standard therapy. Because of the potential role of cellular immune responses in Germany.PhD.the perpetuation of this disease, we elected to treat her with antilymphocyte globulin (ALG), and observed

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“…Thus, treatment of leukemia patients with antibodies to leukemic cells results in the disappearance of reactive membrane antigens (25). Similarly, administration of the monoclonal antibody OKT3 to renal allograft recipients causes a decrease in OKT3+ T cells and the appearance of OKT4+/T3 and OKT8+/ T3 cells in peripheral blood followed by re-expression of the OKT3 determinant after overnight incubation in culture (26). Work is in progress to determine whether such phenomena occur spontaneously in SLE, as is perhaps suggested by the observation of Steinberg and colleagues that brightly IgM-staining cells are selectively "lost" in patients with active disease (27).…”

Section: Okt3 Stainingmentioning

confidence: 99%

Surface antigen specificity of cold‐reactive IgM antilymphocyte antibodies in systemic lupus erythematosus

Yamada

Shaw

Winfield

1985

Arthritis & Rheumatism

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Monoclonal antibodies to known surface antigens on B cells and on resting and activated T cells of various types were used in several approaches to examine the specificity of IgM antilymphocyte antibodies in systemic lupus erythematosus (SLE). Surface determinants that were sought included: T3, T11, Leu-1, Leu-8 (pan-T); T4, T8 (T subset); P2-microglobulin (Pzm); L243, Leu-10 (DR and DS/DC framework, respectively); anti-Tac (interleukin-2 receptor); 5E9 (transferrin receptor); and 4F2, AA1 (other activation antigens). The first strategy was based on inhibition of rosette formation between mouse monoclonal antibody-coated targets and antimouse IgG-coated erythrocytes by SLE sera, either directly at 4°C or after modulation of IgM antilymphocyte antibody-reactive target cell antigen at 37°C. Significant rosette inhibition, defined as >2 standard deviations from the mean value for 10 control sera, was seen only for P2m (13 of 20 SLE sera were positive; inhibition = 1548%). Next, relative fluorescence intensity of lymphocyte staining by monoclonal antibodies was assessed by flow microfluorometry after preincubation of cells with SLE serum at 4°C or after modulation of SLE Submitted for publication April 9, 1984; accepted in revised form July 26, 1984. antibody-reactive antigen. Modulation markedly reduced or eliminated SLE antilymphocyte antibody IgM staining. Except for Pzm, neither cold nor warm temperature preincubations altered the relative fluorescence intensity for the known surface antigens. These data confirm anti-P2m as a common antibody specificity in SLE and suggest that antilymphocyte antibodies in this disorder are not directed to Ia or to certain other defined lymphocyte antigens of functional interest.

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Human in vivo antigenic modulation induced by the anti‐T cell OKT3 monoclonal antibody

Cited by 193 publications

References 24 publications

The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes

The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes

Long‐term immunomodulatory effects of t lymphocyte depletion in patients with systemic sclerosis

Surface antigen specificity of cold‐reactive IgM antilymphocyte antibodies in systemic lupus erythematosus

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