Immunotoxin-Mediated Depletion of CD5+ T Cells from Bone Marrow for Graft-vs.-Host Disease Prophylaxis
Adrian P. Gee in BONE MARROW PROCESSING and PURGING, 2020
We and others have purged the marrow of T cells using monoclonal antibodies (mAb) to the cell surface protein CD5.19–22 CD5 is a human T cell antigen that is found on the majority of mature T cells. It is not found on natural killer (NK) cells, some T cells expressing the γ/δ T cell receptor (TCR), nor a small population of T cells expressing the α/β TCR. By purging the marrow with an anti-CD5 mAb, we spared NK cells and CD-5+ T cells. Normal individuals have from 0 to 27% CD5− T cells in their blood. These are capable of cytotoxic and proliferative responses to alloantigens,23,24 and although CD5− T cells are associated with acute GvHD,19 it was hoped that there would be protective effects on the graft and sparing of the GvL effect that would outweigh the problems of GvHD. In addition, we attempted to increase the intensity of the conditioning regimen to increase both the immunosuppression and antileukemic effects of the therapy.
Mucosal B cells and their function
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
The Peyer's patch component of human GALT is constitutive in humans, as in mice. In humans, constitutive GALT, where clusters of B cells express CD5, can be observed in fetal intestine from around 18 weeks of gestation. Although used to identify the B-1 B-cell lineage in mice, CD5 can be expressed by immature transitional B cells in humans and can be an activation marker on human B cells (Figure 10.3). Indeed, fetal intestinal B cells are large activated cells, although there is no evidence of germinal center formation in the healthy fetal intestine. Like GALT in the postnatal intestine, B cells in fetal GALT infiltrate between the epithelial cells in the FAE, suggesting that recognition of microbial antigens is not required for this localization. However, results in originally germ-free then colonized rodents highlight the role of the microbiota in driving the magnitude of epithelial homing.
Immunophenotypic Markers
Wojciech Gorczyca in Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Among B-cell disorders, CD5 is typically expressed in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) and MCL. B-CLL/SLL differs from MCL by CD23 positivity, although some cases of B-CLL may be CD23− and rare cases of MCL may be CD23+. Therefore, definite differentiation between MCL and CLL should be based on the status of BCL1 (cyclin D1) by FISH or immunohistochemistry. Only a small proportion of DLBCL expresses CD5. Lack of BCL1 (cyclin D1) and SOX11 expression and lack of history of B-CLL/SLL distinguish de novo CD5+ DLBCL from MCL and Richter’s syndrome, respectively. The prognosis of de novo CD5+ DLBCL is markedly worse than that for CD5− DLBCL. The subset of intravascular lymphomas, MZL (MALT lymphoma), and rare cases of LPL shows CD5 expression. CD5+ splenic MZLs do not differ clinically from typical CD5− cases, but may show CD13 expression [53]. Only a very few cases of CD5+ FL have been reported. B-cell ALL (B-ALL), HCL, and BL are CD5−.
Development of chimeric antigen receptors targeting T-cell malignancies using two structurally different anti-CD5 antigen binding domains in NK and CRISPR-edited T cell lines
Published in OncoImmunology, 2018
Sunil S. Raikar, Lauren C. Fleischer, Robert Moot, Andrew Fedanov, Na Yoon Paik, Kristopher A. Knight, Christopher B. Doering, H. Trent Spencer
The CD5-VLR-CAR (previously described).24 was generated using a VLR protein sequence shown to be specific for the CD5 antigen.29 The sequence for the CD5-scFv was generated using a published humanized murine immunoglobulin protein sequence,31 and the cDNA sequence designed to express the scFv was codon optimized for human cell expression. The C-terminus of VH was joined with the N-terminus of VL using a 15 bp linker encoding a glycine and serine pentapeptide repeat (G4 S)332 The entire CD5-scFv sequence totaled 720 bp compared to the shorter 570 bp CD5-VLR sequence. The two CD5 sequences were cloned into the CAR cassette, which is a second generation CAR composed of an N-terminal IL-2 signal peptide followed by the CD5-VLR or -scFV antigen binding domain, the transmembrane and intracellular domains of CD28, and the intracellular signaling domain of CD3ζ (Figure 1A). A bicistronic vector co-expressing eGFP and the CD5-CAR via a self-cleaving 2 A peptide sequence (P2 A) was used to enable selection of positively transduced cells by flow sorting (Figure 1B).
Clinicopathologic significance and therapeutic implication of de novo CD5+ diffuse large B-cell lymphoma
Published in Hematology, 2019
Huifen Tang, Hui Zhou, Juying Wei, Hui Liu, Wenbin Qian, Xiaohui Chen
The pathological sections of all CD5+ DLBCL patients were reviewed by at least 2 pathologists. The tissue section was immunohistochemically stained using the EnVision method. And the pathological data of CD5 positive patients were provided by the pathologists. We use a cutoff of 10% or more of tumor cells with dim to expression for CD5 to be considered positive. According to the Hans algorithm [19], based on immunohistochemical results of CD10, BCL6 and MUM1, GCB subtypes were classified as CD10(+)/BCL6(±)/MUM1(±) or CD10(−)/BCL6(+)/MUM1(−), and the rest is classified as non-GCB subtypes. The cutoffs for positivity were ≥30% for CD10, BCL6, and MUM1 to classify these tumors as germinal center or non-germinal center cell-like immunophenotype. The positive cutoff for BCL2 was ≥50%.
Immunohistochemical and Immunocytochemical Analyses in Patients with Vitreoretinal Lymphoma
Published in Ocular Immunology and Inflammation, 2020
Satoru Kase, Kenichi Namba, Hiromi Kanno-Okada, Masahiro Onozawa, Daisuke Hidaka, Daiju Iwata, Kazuomi Mizuuchi, Takako Fukuhara, Junichi Fukuhara, Nobuyoshi Kitaichi, Yoshihiro Matsuno, Susumu Ishida
Cytological findings of all CB specimens showed relatively large atypical lymphoid cells with a high nuclear/cytoplasmic ratio and necrotic background (Figure 3A). All CB specimens also contained small lymphocytes and macrophages. CD3-positive lymphoma cells were not detected in any of the VRL cases. Immunoreactivity for CD5 was observed in one out of the nine VRL cases examined (11%) (Figure 3B). In contrast, immunoreactivity for CD20, a marker for B cells, was marked in the cell membrane of atypical lymphoid cells in 18 out of 19 eyes with VRL (95%). Reactive small lymphocytes did not show CD20 immunoreactivity (Figure 3C). CD10 immunoreactivity was not observed in the atypical lymphoid cells in 11 cases examined (Figure 3D). Nuclear immunoreactivity for Bcl-6 (Figure 3E) and MUM-1 (Figure 1F) was marked in five out of nine cases (56%) and eight out of nine cases (89%) examined, respectively. One VRL case was negative for Bcl-6, MUM-1, and CD10. Hematoxylin-eosin staining (HE) staining in a CB specimen (Figure 4A) and in a part of the subretinal space of an enucleated eye (Case 1) (Figure 4B) demonstrated similar findings regarding atypical cellular distribution and necrosis.
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