Modulation of lymphocyte function with inhibitory CD2: Loss of NK and NKT cells

Ortaldo, John R.; Mason, Anna; Willette-Brown, Jami; Ruscetti, F. W.; Wine, John W.; Back, Timothy C.; Stull, Terri; Bere, Earl W.; Feigenbaum, Lionel; Winkler‐Pickett, Robin; Young, Howard A.

doi:10.1016/j.cellimm.2007.10.001

Cited by 2 publications

(2 citation statements)

References 32 publications

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“…In these populations, alefacept was found to predominantly decrease CD4 + and CD8 + memory T cells with only a modest depletion of NK cells [41,42]. Although NK cells are uniformly CD2 high [45-47] and therefore should be targeted by alefacept, previous studies have not demonstrated any significant effect [41,42]. However, unlike in psoriasis, solid organ transplant, and type 1 diabetes, our study used a higher dose of alefacept and shorter total course.…”

Section: Discussionmentioning

confidence: 99%

Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

Stenger

Chiang

Haight

et al. 2015

Biology of Blood and Marrow Transplantation

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Transfusion-related alloimmunization is a potent barrier to the engraftment of allogeneic hematopoietic stem cells in patients with nonmalignant diseases (NMDs). Memory T cells, which drive alloimmunization, are relatively resistant to commonly used conditioning agents. Alefacept, a recombinant leukocyte function antigen-3/IgG1 fusion protein, targets CD2 and selectively depletes memory versus naive T cells. Three multiply transfused pediatric patients with NMD received a short course of high-dose i.v. alefacept (.25 mg/kg/dose on days –40 and –9 and .5 mg/kg/dose on days –33, –26, –19, and –12) before undergoing unrelated allogeneic transplant in the setting of reduced-intensity pretransplant conditioning and calcineurin inhibitor–based post-transplant graft-versus-host disease (GVHD) prophylaxis. Alefacept infusions were well tolerated in all patients. Peripheral blood flow cytometry was performed at baseline and during and after alefacept treatment. As expected, after the 5 weekly alefacept doses, each patient demonstrated selective loss of CD2hi/CCR7−/CD45RA− effector memory (Tem) and CD2hi/CCR7+/CD45RA− central memory (Tcm) CD4+ and CD8+ T cells with relative preservation of the CD2lo Tem and Tcm subpopulations. In addition, depletion of CD2+ natural killer (NK) cells also occurred. Neutrophil recovery was rapid, and all 3 patients had 100% sorted (CD3/CD33) peripheral blood donor chimerism by day +100. Immune reconstitution (by absolute neutrophil, monocyte, and lymphocyte counts) was comparable with a cohort of historical control patients. All 3 patients developed GVHD but are all now offimmune suppression and >2 years post-transplant with stable full-donor engraftment. These results suggest that alefacept at higher dosing can deplete both memory T cells and NK cells and that incorporating CD2-targeted depletion into a reduced-intensity transplant regimen is feasible and safe in heavily transfused patients.

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Section: Discussionmentioning

confidence: 99%

Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

Stenger

Chiang

Haight

et al. 2015

Biology of Blood and Marrow Transplantation

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“…CD62L at a higher expression level was benefitial to DC rolling along the vessel walls and transmigrating across the vascular barrier. CD2 is a member of another adhesion receptor family that is widely expressed on leukocyte and mediates intercellular recognition and adhesion [15]. The interaction of CD2 and CD58 mediates recognition between DCs and T lymphocytes and plays an important role in antigen-presenting [5].…”

Section: Discussionmentioning

confidence: 99%

Biorheological changes of dendritic cells at the different differentiation stages

Wang

Chen

Zhang

et al. 2010

Clinical Hemorheology and Microcirculation

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The differentiation, maturation and functioning of Dendritic cells (DCs) are dynamic processes. This study investigated the changes of DCs' migration ability and biorheological properties during their differentiation. Transmigration assay showed that, DCs' migration rate was improved significantly as they differentiate (p < 0.05); NSC (Rac1 blocker) treatment could significantly decrease their migration rates (p < 0.05). Confocal images showed that, F-actin uniformly distributed in monocytes; with DC's differentiation, F-actin began to remodel and gather at the site of dendrites; the images presented surface ruffles and uneven sawtooth-like cytoskeletal structures. Fluorescence polarization analysis showed that, membrane fluidity was increased significantly with DC's differentiation (p < 0.05). CD62L was upregulated significantly (p < 0.05) on the third and ninth days. CD2 was upregulated significantly (p < 0.05) until the seventh day. DC's electrophoretic mobility was increased continuously, especially increased significantly from the third day to the fifth day and the final stage (p < 0.05). These results indicate that there are significant changes in the biorheological properties of DCs during their differentiation.

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Modulation of lymphocyte function with inhibitory CD2: Loss of NK and NKT cells

Cited by 2 publications

References 32 publications

Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

Use of Alefacept for Preconditioning in Multiply Transfused Pediatric Patients with Nonmalignant Diseases

Biorheological changes of dendritic cells at the different differentiation stages

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