Impaired activating receptor expression pattern in natural killer cells from patients with multiple myeloma.
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Gene Expression Regulation, Neoplastic↗
Biomedical subjects
D Olive
Publications and source records attributed to D Olive.
Cleavage stage versus blastocyst stage embryo transfer in assisted conception.
BACKGROUND: In the past decade, advances in the understanding of nutrient requirements of embryos, has led to the evolution of culture media designed to support extended culture of embryos in vitro from the standard procedure of 2 to 3 days (for early cleavage embryo transfer) to 5 to 6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Since the initial widespread introduction of blastocyst culture in 1998, there has been conflicting reports about the clinical benefits of this technique. OBJECTIVES: To determine if blastocyst stage embryo transfers (ETs) affects success rates compared with cleavage stage ETs and investigate what factors may influence this. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials. We also searched the Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. Attempts were made to identify trials from the National Research Register, the Clinical Trials Register and the citation lists of review articles and included trials. The last search date was May 2005. The first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 45 trials that were identified, 16 trials met the inclusion criteria and were reviewed. Primary outcomes were rates of live birth, clinical pregnancy and multiple-pregnancy rates per couple. Secondary outcomes were rates of miscarriage, failure to transfer embryos, freezing, implantation and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using odds ratios (OR) for dichotomous outcomes and weighted mean differences for binary outcomes with 95% confidence intervals (CI). MAIN RESULTS: There was no evidence of a difference in live-birth rate per couple between the two treatment groups (7 RCTs; OR 1.16, 95% CI 0.74 to 1.44 [Day 2/3 34.3% vs. Day 5/6 35.4%]); in the clinical pregnancy rate per couple (15 RCTs; OR 1.05, 95% CI 0.88 to 1.26 [Day 2/3 38.8% vs. 40.3%]) even for good prognosis patients (6 RCTs: OR 96% 1.06 CI 0.83 to 1.34). There was also no difference in multiple-pregnancy rate per couple (12 RCTs; OR 0.85, 95% CI 0.63 to 1.13) particularly in trials where equal numbers of embryos were transferred in both groups (6 RCTs: OR 0.91, 95% CI 0.63 to 1.32). There was no evidence of a difference in high order multiple-pregnancy rates per couple (5 RCTs; OR 0.44, 95% CI 0.15 to 1.33) or miscarriage rate per couple between the two groups (9 RCTs; OR 1.33, 95% CI 0.89 to 2.01). Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.57). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (10 RCTs: OR 3.21, 95% CI 2.15 to 4.81[Day 2/3 3.5% vs D 5/6 10.1%]), but was not significantly different for good prognosis patients (7RCTs, OR 1.58 95% CI 0.65 to 3.82). AUTHORS' CONCLUSIONS: There is no evidence of a difference in live birth or pregnancy outcomes between Day 2 to 3 and Day 5 to 6 transfer of embryos. Blastocyst transfer was associated with an increase in failure to transfer any embryos in a cycle and a decrease in embryo freezing rates. In the absence of data on cumulative live birth rates resulting from fresh and thawed cycles, it is not possible to determine if this represents an advantage or disadvantage.
Blastocyst↗
Evidences for ubiquitination and intracellular trafficking of LAT, the linker of activated T cells.
Current evidences indicate that T cells use protein sorting and degradation to control duration and specificity of T cell receptor (TcR) signalling, including the CD3zeta chain which is ubiquitinated upon TcR triggering. In a previous study, we showed that the Linker of activated T cells (LAT) is present at the plasma membrane and in transferrin-labelled intracellular compartments also containing the CD3zeta chain. Here we show that LAT protein levels are tightly regulated in Jurkat lymphoid T cells likely involving proteasome-dependent degradation, recycling through trans-Golgi/endosome compartments and clathrin-dependent internalisation. We further identify a novel post-translational modification of LAT by ubiquitination that is likely to influence LAT protein stability, intracellular localisation and/or recycling. Our results provide novel molecular and regulatory insights into the function of LAT adapter protein in T cell signalling.
Adaptor Proteins, Signal Transducing↗
Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation.
The reconstitution of the plasmacytoid dendritic cells (PDCs) compartment might influence outcome after allogeneic stem cell transplantation (allo-SCT). Thus, we investigated the impact of blood PDCs measured at the third month after reduced-intensity conditioning (RIC) in 54 patients who received an HLA-identical sibling allo-SCT. The absence of grade II-IV acute graft-versus-host-disease (GVHD) was associated with an improved PDC count at 3 months after RIC-allo-SCT (P=0.003; OR=6.4; 95% CI, 1.9-22). The CD34+ stem cell dose and other lymphoid subsets infused with the allograft did not affect PDC recovery. Although PDC count could not predict death from progression or relapse, patients with a "high" PDC recovery profile had an improved overall survival (OS; P=0.03), in contrast to patients with a "low" PDC recovery profile who had an increased incidence of nonrelapse mortality (GVHD, infections) (P=0.03). The overall incidence of late infections (viral, fungal and bacterial) was significantly higher in the "low" PDC recovery group as compared to the "high" PDC recovery group (59 vs 19%; P=0.002). In a multivariate analysis, only a "high" PDC count was significantly predictive of a decreased risk of death (P=0.04; RR=0.34; 95% CI, 0.12-0.96). Monitoring of PDCs at 3 months after RIC-allo-SCT may be a useful indicator predictor of long-term outcome.
Adolescent↗
[New insights into cytotoxic effector cells].
Cytotoxic immune cells play a role against infectious or tumour invasion. There are two types of cytotoxic cells : those involved in innate or natural immunity (natural killer cells, Tgammadelta lymphocytes, NKT cells) and those involved in the adaptive or acquired immunity (cytotoxic T lymphocytes). Recent advances in immunology have allowed the characterisation of unconventional cytotoxic populations, to better individualise the real cytotoxic cells within the traditional CD8+ T-cell population, and finally to get more insights into the activation of the cytotoxicity properties, in particular with regard to NK cells. The data recently acquired concerning the effector cytotoxic cells contribute to a better understanding of the interactions between the immune system and tumour cells. This may provide rational basis for combined immunotherapy protocols.
Cytotoxicity, Immunologic↗
Uterine leiomyoma and menstrual cycle characteristics in a population-based cohort study.
BACKGROUND: We examined the association of uterine leiomyoma with menstrual cycle characteristics in a population of non-care-seeking women. METHODS: This cross-sectional study uses data from the Seveso Women's Health Study (SWHS), a population-based cohort in Italy. Participants included 341 premenopausal women, 30-60 years old, who had an intact uterus and were not pregnant, lactating, or using oral contraception or intra-uterine devices. We examined the presence of any ultrasound-detected uterine leiomyoma in relation to self-reported menstrual cycle length, flow length and heaviness of flow. The association of leiomyoma number, volume, tissue layer location and axial position with menstrual cycle characteristics was also examined. RESULTS: Uterine leiomyomata were detected in 73 women (21.4%). After adjustment for covariates, the presence of a leiomyoma was not significantly related to menstrual cycle length, flow length or heaviness of flow [odds ratio (OR) for scanty flow =1.9, 95% confidence interval (CI) 0.8-4.3; OR for heavy flow =1.3, 95% CI 0.7-2.5; relative to moderate flow]. Number, volume, tissue layer location (subserosal or intramural) and axial position (anterior or posterior) of the leiomyoma were also not related to menstrual cycle characteristics. CONCLUSION: In this Italian population of women not seeking gynaecological care, menstrual characteristics are not related to leiomyoma.
Adult↗
Cytomegalovirus-specific immune recovery following allogeneic HLA-identical sibling transplantation with reduced-intensity preparative regimen.
Cytomegalovirus (CMV) represents a major cause of morbidity after allogeneic stem cell transplantation (allo-SCT). Using interferon-gamma-enzyme-linked immunospot (ELISPOT) assay and HLA-peptide tetramers, we analysed 54 patients who received a reduced-intensity conditioning regimen, including fludarabine, busulphan and antithymocyte globulin (ATG), with the aim of defining essential elements of protective immunity to CMV. The cumulative incidence of CMV positive antigenaemia was 37% occurring at a median of 43 days (range, 7-104) after allo-SCT. In univariate analysis, conditioning regimen (ATG dose) and graft characteristics (graft source and CD3+ T-cell dose) significantly influenced CMV-specific immune recovery. A significant correlation (P=0.000002) was found between CMV-specific T cells detected by IFN-gamma ELISPOT assay and pp65-specific CD8+ T-cell frequency quantified by tetramers. CMV-specific CD8+ T cells presented a phenotype of effector cells (perforin and 2B4 positive). In multivariate analysis, bone marrow (BM) as a graft source was the only variable associated with an increased risk of CMV positive antigenaemia (P=0.0001) in line with the ELISPOT assay showing a higher frequency of functional CMV-specific effectors within peripheral blood stem cell grafts as compared to BM. Thus, early monitoring of CMV-specific immune recovery using sensitive new tools might prove useful for patient management after allo-SCT.
Adult↗
Abundant expression of fibronectin is a major feature of leukemic dendritic cells differentiated from patients with acute myeloid leukemia.
Dendritic cells (DCs) are the most potent antigen-presenting cells responsible for the initiation of primary immune responses, playing a key role in eliciting effective antitumor immune responses. We reported previously that leukemic blasts from selected patients with acute myeloid leukemia (AML) were able to differentiate in vitro into cells with DC features. In order to identify genes differentially expressed in leukemia-derived DCs (AML-DCs), a polymerase chain reaction (PCR)-based subtraction approach was applied using cDNA from AML-DCs and monocyte-derived DCs from healthy donors as competitors. In the 548 sequences analyzed, 80% corresponded to fibronectin (FN) gene fragments. Overexpression of FN in AML-DCs was demonstrated both by semiquantitative PCR analysis and by immunostaining. In addition, we could show that FN was secreted by AML-DCs. Indeed, FN overexpression was already detectable in AML blasts of M4 and M5 subtype, and was significantly induced during DC differentiation after culture. Although the molecular events leading to overexpression of FN and the in vivo relevance of this phenomenon remain to be resolved, leukemic DCs appear to have specific patterns of differentiation, warranting stringent biological and cellular monitoring for the development and testing of leukemic DC-based immunotherapeutic strategies.
Acute Disease↗
Altered splicing in hematological malignancies reveals a tissue-specific translational block of the Src-family tyrosine kinase fyn brain isoform expression.
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Alternative Splicing↗
New approaches in the immunotherapy of haematological malignancies.
Advances in the management of haematological malignancies have allowed to obtain improved remission rates. Nonetheless, relapses impair these results and justify the search for novel therapeutic strategies. Clinical data demonstrate that the immune system plays an important role in the control of haematological malignancies. An increased frequency of haematological malignancies is observed in immunodeficiency states. Reversal of the immunosuppression is sometimes sufficient to induce tumour regression (withdrawal of cyclosporine in post-transplant lymphoproliferations, highly active anti-retroviral treatment in human immunodeficiency virus related Kaposi's disease). Another line of evidence for the involvement of the immune system in the anti-tumour response comes from the observation of spontaneous anti-tumour responses that parallel the occurrence of paraneoplastic immune-mediated syndromes. Finally, the efficiency of allogeneic transplantation in the haematological field has been clearly demonstrated to depend on the immune-mediated graft vs. leukaemia effect. Nonetheless, tumours develop in immune competent patients because of various tumour escape mechanisms, such as loss of human leucocyte antigen class I antigens, absence of target recognition by deficient adhesion/co-stimulatory molecule expression, tumour cell counterattack against immune effectors, direct (contact-dependent) or indirect (cytokine-mediated) impairment of T-lymphocyte activation. Novel immunotherapy approaches are now orientated in a convergent direction, i.e. the reversal of immune escape mechanisms either via the correction of deficient phases of the immune response or by the amplification of physiological mechanisms.
Antibodies, Monoclonal↗
DOK4 and DOK5: new Dok-related genes expressed in human T cells.
Dok proteins are adapter proteins involved in signal transduction. Several intracellular proteins expressed in lymphocytes meet the criteria of membrane-associated adapter proteins such as members of the Dok family. To understand the role and the formation of multiprotein networks involving Dok proteins in T lymphocytes, we search for potential additional members of this family. Here, we describe the two new human dok-related genes DOK4 and DOK5 and present data showing the expression of DOK4 and DOK5 genes in T cells. These genes are the orthologues of mouse Dok4 and Dok5 genes. Based on analysis of phylogenetic trees and exon/intron structure of Dok family members, DOK4 and DOK5 define a subfamily within dok genes distinct from DOK1, DOK2 and DOK3. So, Dok-4 and Dok-5 molecules constitute a new group of adapter proteins in T cells, requiring further functional analysis.
Adaptor Proteins, Signal Transducing↗
Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen.
In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P=0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (>2 mg/kg) represented the major risk factor for bacteremia (P=0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.
ABO Blood-Group System↗
Stimulation of non-Hodgkin's lymphoma via HVEM: an alternate and safe way to increase Fas-induced apoptosis and improve tumor immunogenicity.
Stimulation by CD40 ligand (L) improves B-cell malignancy immunogenicity, and also induces proliferative signals. To avoid these tumorigenic effects, we studied an alternate way of tumor-cell stimulation by homologous to lymphotoxin, inducible expression, competing for GpD of herpesvirus, which binds to the herpesvirus entry mediator (HVEM), and is expressed on T-lymphocytes (LIGHT), the ligand for HVEM, a new member of the tumor necrosis factor (TNF)/TNF-receptor (-R) family. HVEM is constitutively expressed on the surface of tumor B cells. We focused our attention on mantle cell lymphoma, a subtype of B-cell malignancy of poor prognosis. Triggering by LIGHT, in contrast to CD40L stimulation, did not increase lymphoma proliferation nor decrease chemotherapy entrance. We observed an upregulation of the TNFR apoptosis-inducing ligand Fas, and in contrast to CD40L-induced protection, an enhancement of lymphoma sensitivity to Fas-induced apoptosis. LIGHT triggering increased lymphoma cell recognition in a mixed lymphocyte response. In conclusion, LIGHT-mediated triggering renders B-cell lymphomas more immunogenic and sensitive to apoptosis, without inducing proliferation. Since LIGHT triggering also enhances the functions of T-lymphocytes and dendritic cells, it could be a unique way to restore an efficient cancer control by its pleiotropic effects on immune effectors and tumor cells.
Apoptosis↗
Interaction with simian Hck tyrosine kinase reveals convergent evolution of the Nef protein from simian and human immunodeficiency viruses despite differential molecular surface usage.
Simian and human immunodeficiency virus type 1 (SIV and HIV-1) Nef proteins are thought to use different molecular surfaces to mediate the protein-protein interactions required for their otherwise similar functions. This genetically separable function suggests convergent evolution of primate lentiviruses and/or structural differences between human and nonhuman primate cellular target proteins. However, such comparative molecular analyses have not been undertaken so far using the respective natural host-derived cellular targets. We cloned simian Src family kinase Hck and analyzed structurally and biochemically its interaction with SIV Nef.
Amino Acid Sequence↗
Laparoscopic surgery for subfertility associated with endometriosis.
BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched Feb 2000), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2000), MEDLINE (1966-July 2001), EMBASE (1980-July 2001), the National Research Register (Issue 1, 2000) and reference lists of articles. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies had data appropriate for inclusion within the review. These studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses and complications of surgery. MAIN RESULTS: Meta-analysis of the two randomised trials show improvement in infertility associated with endometriosis with laparoscopic surgery. The largest trial (Marcoux 1997) clearly supports this outcome with an increased chance of pregnancy (OR 2.03, 95% CI 1.28 to 3.24) and ongoing pregnancy rate after 20 weeks (OR 1.95, 95% CI 1.18 to 3.22) but the smaller trial (Gruppo Italiano 1999) does not show benefit (pregnancy OR 0.76, 95% CI 0.31 to 1.88; livebirth OR 0.85, 95% CI 0.32 to 2.28). Combining ongoing pregnancy and live birth rates there was a statistically significant increase with surgery (OR 1.64, 95% CI 1.05 to 2.57). REVIEWER'S CONCLUSIONS: The use of laparoscopic surgery in the treatment of minimal and mild endometriosis may improve success rates. The relevant trials have some methodological problems and further research in this area is needed.
Endometriosis↗
Cleavage stage versus blastocyst stage embryo transfer in assisted conception.
BACKGROUND: Despite numerous advances in the field of in vitro fertilisation (IVF), many of the widely applied embryo culture techniques and resulting implantation rates have remained relatively unchanged since the first treatment was performed in the mid 1970's. Recent advances in the understanding of nutrient requirements of embryos, have led to a renaissance of extending their culture from the standard procedure of 2-3 days (early cleavage embryo transfer) to 5-6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Numerous reports on the clinical benefits of blastocyst culture have led to the worldwide introduction of this technique, despite a deficiency of conclusive evidence to do so. OBJECTIVES: Primary: To determine if blastocyst stage embryo transfers (ET's) result in higher success rates, than cleavage stage embryo transfers. Secondary: To assess the overall embryo utilisation rate of both techniques. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, and Bio extracts were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. The first or corresponding author of each included trial was also contacted for additional information. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 29 trials that were identified, ten trials met the inclusion criteria and were reviewed. Primary outcomes were rates of; live birth, clinical pregnancy and implantation per woman. Secondary outcomes were rates of; miscarriage, monozygotic twinning, embryo freezing, embryo utilisation, cancellation, multiple pregnancy and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: There was no significant difference between the two treatment groups in live birth rate, although this was reported by only one quasi-random trial (Peto OR 1.59, 95% CI 0.80, 3.15). There was also no evidence of a difference in pregnancy rate (both overall and subgroups) between the two groups for pregnancy rate per couple randomised (4 RCTs: Peto OR 0.86, 95% CI 0.57, 1.29). There was also no suggestion of an overall difference in implantation rates per embryo's transferred although it was impossible to calculate valid confidence intervals from published data (Day 2/3 17.1% vs Day 5/6 18.9%). The subgroup of sequential media trials suggested higher implantation rate for blastocyst transfer (Day 2/3 22.6% vs Day 5/6 32%). The miscarriage rate was no different between the two groups (1 RCT, Peto OR 1.66, 95% CI 0.41, 6.81). The RCTs reporting embryo freezing showed no difference (Peto OR 1.71, 95% CI 1.00, 2.94), however the two quasi-random trials showed a significant difference in favour of the Day 2/3 group (Peto OR 2.99, 95% CI 1.88, 4.75). Embryo transfer cancellation rates were significantly higher in the Day 5/6 group (5 RCTs: Peto OR 0.57, 95% CI 0.40, 0.83). There was no significant difference in the rate of multiple pregnancies or the rate of high order pregnancies (3 RCTs, Peto OR 0.58, 95% CI 0.30, 1.12)(2 RCTs, Peto OR 7.88, 95% CI 0.49, 126.30 respectively). REVIEWER'S CONCLUSIONS: Overall this review of the best available evidence based on data from randomised controlled trials, suggests that to date little difference in the major outcome parameters has been demonstrated between early embryo transfer and blastocyst culture. Collectively, the increase in cancellation and the possible decrease in cryopreservation rates suggest that the routine practice of blastocyst culture should be offered to patients with caution. The subgroup of trials employing sequential media, did however demonstrate a substantial improvement in implantation rates and similar pregnancy rates, despite the transfer of less embryos. Whether this trend will culminate in convincing higher live birth rates per woman, has yet to be validated.
Blastocyst↗
A novel mechanism of antitumor response involving the expansion of CD3+/CD56+ large granular lymphocytes triggered by a tumor-expressed activating ligand.
We describe a patient with acute myeloid leukemia (AML) who developed polyclonal large granular lymphocyte (LGL) proliferation. The reciprocal evolution of AML and LGLs suggested that these LGLs had an anti-tumor activity. The patient's LGLs killed autologous leukemia cells in a different way to classical T lymphocyte-mediated cytotoxicity since it did not rely on the recognition of target antigens presented by major histocompatibility complex (MHC) class I molecules by the CD3/TcRalphabeta complex. This killing was also different from natural killer (NK)-mediated cytotoxicity, which depends on the absence of MHC class I molecule recognition by NK inhibitory receptors. The LGLs were polyclonal, had a CD3+/CD8+/CD56+ phenotype, and did not express the natural killer cell receptors (NKRs) for MHC class I molecules. The LGLs did not express the NK-specific activating natural cytotoxicity receptors but expressed the 2B4 non-MHC restricted triggering receptor, whose ligand CD48 was expressed by leukemic cells and normal bone marrow cells. The 2B4 receptor participated in the ability of LGLs to lyse patient's leukemia. This represents a novel function for 2B4 in man, since this molecule, at variance with the murine system, was considered not to have direct effects on CD8+ T cell-mediated cytotoxicity. This case report allowed us to describe a novel T lymphocyte-mediated anti-tumor mechanism which relied on (1) the abnormal expansion of the rare 2B4-positive CD3+/CD8+/CD56+ T lymphocyte subset, (2) an as yet undescribed cytotoxicity mechanism in man which depended on 2B4 molecule. The relevance of this observation in human cancer immunotherapy has to be further investigated.
Acute Disease↗
Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis.
Large granular lymphocyte (LGL) proliferation typically follows a chronic course during which major features are cytopenia and immune abnormalities. Elevated numbers of LGL were reported in a few cases following allogeneic stem cell transplantation (allo-SCT). In this report, we present a retrospective analysis of LGL cases that occurred following allo-SCT in a cohort of 201 consecutive patients transplanted over a period of 7 years. Six cases were identified and LGL expansion occurred more frequently following a reduced fludarabine and anti-T lymphocyte globulin-based preparative regimen (4 cases/49), than after a conventional myeloablative regimen (2 cases/152). Expansion of LGL was seen between 3 and 15 months following allo-SCT. Hematopoiesis, with mild to severe cytopenia, was a favored target for LGL. Autoimmune manifestations including polyarthritis and hypergammaglobulinemia were also observed. LGL proliferation was observed in the context of chronic antigenic stimulation associated with recurrent viral infections especially CMV. Moreover, five out of these six high risk patients achieved a long-term complete remission concomitant or following LGL expansion. These data suggest that LGL might be a subset of effector lymphocytes which may participate to the graft-versus-tumor effect.
Adult↗