B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection

Aim: Chronic active antibody-mediated rejection (CAABMR) is an important cause of late-stage renal allograft loss. Early inflammatory events such as acute rejection and infection after transplantation are considered to be the risk factors of de novo donor-specific antibody (dnDSA) production. In this study, we investigated the relationship between predisposing T-cell-mediated rejection and dnDSA-positive CAABMR. Methods: We recruited 365 patients who underwent ABO-compatible renal transplantation at our hospital. Among them, 16 patients diagnosed as having dnDSA-positive CAABMR were designated as a CAABMR group, and 38 randomly selected patients were designated as a control group. All biopsies from 1 month after transplantation were included in the study. The presence or absence of borderline changes (BLCs), acute T-cell-mediated rejection (ATMR), microvascular inflammation (MVI), and C4d positive on peritubular capillaries (C4d-P) was examined. Results: In the CAABMR group, BLC/ATMR was found in 12 cases (75%), and the mean duration until appearance of BLC/ATMR was 282.7 ± 328.7 days. C4d-P was found in 11 cases (68.8%), and the mean duration until its appearance was 1,432 ± 1,307 days. MVI was found in all cases, and the mean duration until its appearance was 1,333 ± 1,126 days. The mean duration until diagnosis of CAABMR was 2,268 ± 1,191 days. In the control group, BLC/ATMR was found in 13 cases (34.2%), and the mean duration until the appearance of BLC/ATMR was 173.1 ± 170.4 days. C4d-P was found in 2 cases (5.3%), and the durations until its appearance were 748 and 1,881 days. No cases of MVI were found in the control group. The frequency of BLC/ATMR was significantly higher in the CAABMR group (p < 0.01). Conclusion: Preceding BLC/ATMR is associated with the development of CAABMR with dnDSA.

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Novel leukaemia markers

Bioscience Reports ◽

10.1007/bf01204349 ◽

1995 ◽

Vol 15 (6) ◽

pp. 463-468

Author(s):

Kingsley J. Micklem

Keyword(s):

Monoclonal Antibodies ◽

T Cell ◽

Recombinant Protein ◽

Follicular Lymphoma ◽

B Lymphocytes ◽

Synthetic Peptide ◽

Paraffin Sections ◽

Hematologic Disorders ◽

Polyclonal Antisera ◽

Chromosomal Defects

Using synthetic peptide or recombinant protein as immunising antigens we have produced monoclonal antibodies and polyclonal antisera directed against targets of particular interest in leukaemia diagnosis. In this way we have prepared reagents which recognise all T or all B lymphocytes in routinely fixed paraffin sections which are unique in this respect. We have also produced monoclonal antibodies to molecules potentially involved in specific neoplastic transformations, implicated by virtue of the involvement of their genes in chromosomal defects in these neoplasms. In particular, we have produced antibodies recognising bcl-2, involved in follicular lymphoma, tal-1, involved in T-cell acute leukaemias and HRX involved in a variety of hematologic disorders. The application of these reagents to diagnosis has so far proved useful. In addition their use outside the field of leukaemia diagnosis has proved to be even more important in some cases.

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In vivo expression of interleukin-8, and regulated on activation, normal, T-cell expressed, and secreted, by human germinal centre B lymphocytes

Immunology ◽

10.1046/j.1365-2567.2003.01745.x ◽

2003 ◽

Vol 110 (3) ◽

pp. 296-303 ◽

Cited By ~ 16

Author(s):

Jennifer C. Sims-Mourtada ◽

Liliana Guzman-Rojas ◽

Roberto Rangel ◽

Dat X. Nghiem ◽

Stephen E. Ullrich ◽

...

Keyword(s):

T Cell ◽

B Lymphocytes ◽

Germinal Centre ◽

Interleukin 8 ◽

In Vivo Expression

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MO243STUDY ON THE EFFECT AND MECHANISM OF NOVEL REGULATORY T CELL (CD4+CD126LOWFOXP3+ TREG) IMMUNOTHERAPY IN LUPUS NEPHRITIS*

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Zhenjian Xu ◽

Junzhe Chen ◽

Anping Xu

Keyword(s):

T Cell ◽

Lupus Nephritis ◽

Signaling Pathway ◽

B Lymphocytes ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Proliferation And Differentiation ◽

Inflammatory State

Abstract Background and Aims Our previous study found a new regulatory T cell subpopulation, CD4+CD126lowFoxp3+ regulatory T cells (CD4+CD126lowFoxp3+ Treg). This cell can maintain a stable immune regulatory function in the inflammatory state. Through in vivo and in vitro experiments, we have confirmed that CD4+CD126lowFoxp3+ Treg has an immunotherapeutic effect on T cell-mediated mouse models of autoimmune diseases such as colitis and collagen-induced arthritis (CIA). Further experimental studies showed that CD4+CD126lowFoxp3+ Treg could reduce the kidney injury caused by autoantibodies and prolong the survival time of lupus mice. However, the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in lupus nephritis is not clear. The purpose of this study was to explore the mechanism of CD4+CD126lowFoxp3+ Treg immunotherapy in mice with lupus nephritis. Method In vitro experiments CD4+CD126lowFoxp3+ Treg or CD4+CD126lowFoxp3+ Treg pretreated with PD-1 inhibitor were co-cultured with T or B lymphocytes of lupus mice under different in vitro culture condition. The expression levels of Akt and mTOR of Treg in each group were measured under immunoinflammatory conditions. To observe the effects and differences of Treg groups on the activation, proliferation and differentiation of T or B cells and other immunomodulatory effects. In vivo experiments CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) and CD4+CD126lowFoxp3+ Treg (2 × 106/mouse) pretreated with PD-1 inhibitor and PBS were injected into NZM2328 lupus mice, respectively. After cell injection, urine protein was measured weekly. Autoantibody expression in lupus mice was measured every two weeks. The effects of Treg on the proliferation and differentiation of T/B cells in lupus mice were observed. The therapeutic effects of Treg on lupus mice were observed. Results Compared with CD4+CD126lowFoxp3+ Treg, the expression of Akt and mTOR increases in PD-1 inhibitors pretreatment cells. The activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vitro, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-mTOR signaling pathway through PD-1 in in vitro. Compared with CD4+CD126lowFoxp3+ Treg, the activation, proliferation and differentiation functions of T or B lymphocytes of lupus mice were significantly weakened by immunosuppression of PD-1 inhibitors pretreated Treg in vivo. And its therapeutic effect on lupus mice was ineffective, indicating that CD4+CD126lowFoxp3+ Treg may inhibit Akt-MTOR signaling pathway through PD-1 in vivo. Conclusion CD4+CD126lowFoxp3+ Treg may inhibit the Akt-mTOR signaling pathway by expressing PD-1, and maintain stable immunomodulatory function in the inflammatory state, thus producing immunotherapeutic effect on lupus nephritis mice.

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Requirement for T cells in the production of migration inhibitory factor.

Journal of Experimental Medicine ◽

10.1084/jem.142.5.1306 ◽

1975 ◽

Vol 142 (5) ◽

pp. 1306-1311 ◽

Cited By ~ 25

Author(s):

B R Bloom ◽

E Shevach

Keyword(s):

T Cells ◽

T Cell ◽

B Lymphocytes ◽

Cell Function ◽

Plaque Assay ◽

Quantitative Measure ◽

Immune Response Gene ◽

Migration Inhibition ◽

Qualitative Assay ◽

Gene Restriction

The question whether B lymphocytes are capable of being activated by antigen in the absence of functional T cells was investigated in a model that excludes participation of T cells by virtue of an immune response gene restriction. Strain 2 guinea pigs are capable of responding to immunization with DNP-PLL, whereas strain 13 animals are not. In the present experiments, animals of both strains were immunized with DNP-PLL complexed to ovalbumin (DNP-PLL-Ova) under conditions in which equal titers of antibodies to DNP were produced by both strains. The failure of T cells of strain 13 animals to respond to DNP-PLL was confirmed by the virus plaque assay. While spleen cells from both strains produced MIF after stimulation with DNP-PLL-Ova, in response to DNP-PLL only strain 2 spleens were able to produce MIF. Cells from neither strain could be activated by DNP-guinea pig albumin to produce MIF. We conclude that B lymphocytes are incapable of being stimulated by antigen in the absence of T cells, and that MIF production is a thymus-dependent response. While the results indicate that MIF production is a valid qualitative assay for T-cell competence, since MIF can be produced by B and T cells, the degree of migration inhibition cannot be regarded as a quantitative measure of T-cell function.

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CD5+ B Lymphocytes and T-cell Subsets in a Case of Juvenile Rheumatoid Arthritis

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1992.tb24663.x ◽

1992 ◽

Vol 651 (1) ◽

pp. 564-569 ◽

Cited By ~ 7

Author(s):

F. AMBROGI ◽

L. RICCIARDI ◽

P. NUTINI ◽

R. VANACORE

Keyword(s):

Rheumatoid Arthritis ◽

T Cell ◽

Juvenile Rheumatoid Arthritis ◽

B Lymphocytes ◽

T Cell Subsets

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Pure T-cell-mediated rejection following kidney transplant according to the response to treatment in the era of antibody-mediated rejection

Korean Journal of Transplantation ◽

10.4285/atw2020.op-1233 ◽

2020 ◽

Vol 34 (1) ◽

pp. S15-S15

Author(s):

Hyunwook Kwon ◽

Sung Shin ◽

Duck Jong Han ◽

Young Hoon Kim ◽

Joo Hee Jung ◽

...

Keyword(s):

T Cell ◽

Kidney Transplant ◽

Response To Treatment ◽

Antibody Mediated Rejection

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