The Influence of T Cell Depletion on Recovery of T Cell Proliferation to Herpesviruses and Candida After Allogeneic Bone Marrow Transplantation

Gast, Gijsbert C. de; Gratama, Jan W.; Verdonck, Leo F.; Heugten, J. G. Van; Zwaan, F. E.; Phillips, D. I. M.; Mudde, GC

doi:10.1097/00007890-198907000-00026

Cited by 17 publications

(15 citation statements)

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“…Beyond that, the concept of a complete T cell depletion to preserve a graft-versus-leukaemia effect and to generate a sufficient host-immune system after allogeneic transplantation has been abandoned. 26,27 However, to investigate purging efficacy for processing aphereses from patients with nonHodgkin's lymphoma, these experiments should be repeated determining the percentage of B and T lymphocytes before and after selection. The necessity of investigating these questions was recently supported by a paper from Hawkins et al, 28 who described -in contrast to our resultsthe highest purity of CD34 + cells selected from materials obtained from CML patients after immunoaffinity selection.…”

Section: Discussionmentioning

confidence: 99%

Purging and haemopoietic progenitor cell selection by CD34+ cell separation

Krüger

Gruber

et al. 1998

Bone Marrow Transplant

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The median tumour cell reductions in log steps were 3.7 (2.9-4.3) (n ‫؍‬ 13) (Isolex-50), 3.5 (2.6-4.3) (n ‫؍‬ 13) (MiniMACS) and 1.5 (0.9-2.9) (n ‫؍‬ 17) (Ceprate-LC). Results were compared statistically by univariate analysis. Purity was significantly (P Ͻ 0.05) better after Mini-MACS selection. Recovery rates were significantly different between all devices tested. Tumour cell purging was superior after immunomagnetic separation (P Ͻ 0.001). Tumour cell purging is a main objective of CD34 + selection in the autologous setting. High-dose chemotherapy supported by autologous stem cell reinfusion for treatment of metastatic and high-risk female breast cancer is currently under investigation in several American and European studies. 1,2,3 Tumour cell contamination of autologous stem cell products has been described using immunocytochemistry, reverse transcriptase PCR and cell culture techniques in approximately one third of harvests with a range from 0% to 100%. [4][5][6][7] The clonogenic and metastatic potential of tumour cells isolated from blood and autografts was demonstrated in cell culture assays and in nude mice. [8][9][10] The metastatic potential of accidentally retransplanted tumour cells could be investigated by gene marking of autografts prior to infusion followed by the detection of marked cells after relapse. 11 However, due to the poor transduction efficacy of epithelial cancer cells by gene transfer, a negative result would not exclude the possibility of relapse induction by accidentally reinfused tumour cells. Different approaches have been described to purge autografts of tumour cells. 12 A major problem of purging procedures using cytotoxic agents is the damage to haemopoietic progenitor cells with subsequent delay of engraftment, an increased incidence of severe infections due to prolonged neutropenia and bleeding complications due to thrombocytopenia. [13][14][15] Haemopoietic cells necessary for recovery after highdose therapy and progenitor support express the CD34 antigen on their surface. 16 These cells can easily be enriched by immunological methods using anti-CD34 antibodies and separation by biotin-streptavidin immunoaffinity or magnetic separation with paramagnetic microbeads. Rapid and safe engraftment after reinfusion of enriched CD34 + cell fractions has been described by several investigators after allogeneic and autologous transplantation. 17,18 The immunologic selection of CD34-positive cells has no toxic side-effects on haemopoietic stem cells and progenitors without prolongation of cytopenia after reinfusion.Furthermore, CD34 positive-cell selection is a promising approach to reducing the incidence or mitigating the severity of graft-versus-host-disease in the allogeneic setting by adjusted or nearly complete T cell depletion. However, the major rationale for CD34-positive cell selection in autologous marrow and stem cell transplantation is a reduction or removal of contaminating tumour cells accidentally coharvested during leukapheresis to avoid their reinfusion after high-d...

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Section: Discussionmentioning

confidence: 99%

Purging and haemopoietic progenitor cell selection by CD34+ cell separation

Krüger

Gruber

et al. 1998

Bone Marrow Transplant

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“…However, functional recovery of the T cell system after T cell-depleted allogeneic BMT has been demonstrated (47,48), and both donor and recipient DC may contribute to the reconstitution of the T cell repertoire in transplantation through distinct pathways of Ag presentation (49). Interestingly, it has been reported that T cell reactivity to Candida readily recovered after T cell-depleted allogeneic BMT, and the fact that recovery was related to the absence of antifungal prophylactic measures indicates that anticandidal reactivity of residual T cells could be maintained through continuous exposure to the fungus (50).…”

Section: Figurementioning

confidence: 99%

Dendritic Cells Pulsed with Fungal RNA Induce Protective Immunity toCandida albicansin Hematopoietic Transplantation

Bacci

Montagnoli

Perruccio

et al. 2002

The Journal of Immunology

120

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Immature myeloid dendritic cells (DC) phagocytose yeasts and hyphae of the fungus Candida albicans and induce different Th cell responses to the fungus. Ingestion of yeasts activates DC for production of IL-12 and Th1 priming, while ingestion of hyphae induces IL-4 production and Th2 priming. In vivo, generation of antifungal protective immunity is induced upon injection of DC ex vivo pulsed with Candida yeasts but not hyphae. In the present study we sought to determine the functional activity of DC transfected with yeast or hyphal RNA. It was found that DC, from either spleens or bone marrow, transfected with yeast, but not hyphal, RNA 1) express fungal mannoproteins on their surface; 2) undergo functional maturation, as revealed by the up-regulated expression of MHC class II Ags and costimulatory molecules; 3) produce IL-12 but no IL-4; 4) are capable of inducing Th1-dependent antifungal resistance when delivered s.c. in vivo in nontransplanted mice; and 5) provide protection against the fungus in allogeneic bone marrow-transplanted mice, by accelerating the functional recovery of Candida-specific IFN-γ-producing CD4+ donor lymphocytes. These results indicate the efficacy of DC pulsed with Candida yeasts or yeast RNA as fungal vaccines and point to the potential use of RNA-transfected DC as anti-infective vaccines in conditions that negate the use of attenuated microorganisms or in the case of poor availability of protective Ags.

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“…Development of positive lymphocyte proliferation to Candida and herpes simplex virus is dependent of prophylaxis with amphotericin B and acyclovir [4]. Prophylaxis with anti-fungal, anti-microbial and anti-viral drugs delays exposure to antigens and therefore can delay immune responses to these antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Influence of T cell depletion of the donor marrow on recovery of lymphocyte proliferative responses after allogeneie BMT has indicated that in the early post-BMT period, development of lymphocyte proliferation to CMV is important in prevention of active CMV infeetion [4]. CMV pneumonia was more often seen in patients with negative lymphocyte proliferation to CMV 3 months after BMT, who had received partially T cell depleted marrow, compared with patients receiving undepleted marrow, in whom lymphocyte proliferation to CMV became positive earlier after BMT.…”

Section: Introductionmentioning

confidence: 99%

Evidence for transfer of cellular and humoral immunity to cytomegalovirus from donor to recipient in allogeneic bone marrow transplantation

Boland

Vlieger

Ververs

et al. 1992

Clinical and Experimental Immunology

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SUMMARYIn order to study the importance ofthe immune status ofthe donor in the development of immunity after allogeneic bone marrow transplantation (BMT), we monitored 23 cytomegalovirus (CMV) antibody-positive BMT recipients for humoral and cellular immunity to CMV, of whom 12 had a CMV antibody-positive and 11 a CMV antibody-negative marrow donor. Lymphocyte proliferation to CMV recovered significantly earlier after BMT in recipients of marrow from a CMV+ donor (10-4 weeks after BMT) compared with the recipients of marrow from CMV" donors (16-7 weeks after BMT, /'<0-05). This seemed to be specific, as lymphocyte proliferation to phytohaemagglutinin and Candida were not different between the two groups. IgM responses after active infection were seen in both groups, but initial IgG rises without IgM were seen only in recipients of marrow from CMV+ donors (/'<0-05). Lymphocyte proliferative or humoral immune responses to CMV were not detected in any ofthe patients in a control group consisting of nine CMV" recipients. These results indicate that T cell memory to CMV is transferred with donor marrow from CMV+ donors, leading in most patients to direct IgG anti-CMV responses and to quicker recovery of cellular immunity to CMV.

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The Influence of T Cell Depletion on Recovery of T Cell Proliferation to Herpesviruses and Candida After Allogeneic Bone Marrow Transplantation

Cited by 17 publications

References 0 publications

Purging and haemopoietic progenitor cell selection by CD34+ cell separation

Purging and haemopoietic progenitor cell selection by CD34+ cell separation

Dendritic Cells Pulsed with Fungal RNA Induce Protective Immunity toCandida albicansin Hematopoietic Transplantation

Evidence for transfer of cellular and humoral immunity to cytomegalovirus from donor to recipient in allogeneic bone marrow transplantation

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