RESUMO
The NCR receptors play a fundamental role in the cytotoxicity mediated by NK cells against tumor cells. In the current study, we investigated possible HIV/AIDS-related changes in the expression of the NCR receptors comparing healthy donors, HIV/AIDS patients, and HIV/AIDS patients with cancer (HIV/AIDSWC). The NCRs were quantified in NK cells (NK(dim) and NK(bright)) and T lymphocytes from peripheral blood samples by flow cytometry. We found a significant decrease in the frequency of NK cells expressing NKp46 in HIV/AIDS group (p = 0.0012). There was a decrease in the frequency of NK cells expressing NKp46 in the HIV/AIDSWC group; however, this was not statistically significant. We found a significant decrease in the frequency of NK cells expressing NKp30 in the HIV/AIDS group (p = 0.0144). There was a decrease in the frequency of NK cells expressing NKp30 and in the HIV/AIDSWC group, but this was not statistically significant. There were no changes in the distribution of NK cells and their subtypes in both groups.
Assuntos
Infecções por HIV/imunologia , Células Matadoras Naturais/imunologia , Receptor 1 Desencadeador da Citotoxicidade Natural/imunologia , Receptor 3 Desencadeador da Citotoxicidade Natural/imunologia , Neoplasias/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45(low) CD33(high), CD117âº, CD13(-/+), HLA Dr(high), CD123(high), and CD203c⺠blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity.In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation.
Assuntos
Neoplasias da Mama/terapia , Proteínas de Ligação a DNA/metabolismo , Leucemia Mieloide/etiologia , Transplante de Células-Tronco/efeitos adversos , Proteína Grupo D do Xeroderma Pigmentoso/metabolismo , Antineoplásicos/uso terapêutico , Análise Citogenética , Proteínas de Ligação a DNA/genética , Evolução Fatal , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Leucemia Mieloide/patologia , Repetições de Microssatélites , Pessoa de Meia-Idade , Polimorfismo Genético , Transplante Homólogo , Proteína Grupo D do Xeroderma Pigmentoso/genéticaRESUMO
Most studies on natural killer (NK) cells and aging have focused on overall cell numbers and global cytotoxic activity. NK cell functions are controlled by surface receptors belonging to three major families: killer cell immunoglobulin-like receptors (KIRs), natural cytotoxicity receptors (NCRs), and C-type lectins. The expression of these receptors was investigated from childhood through old age in T, NKT- and NK cells and also in the CD56(dim) (cytotoxic) and CD56(bright) (responsible for cytokine production) NK cell subsets. A decrease in the expression of activating receptors (NKp30 and NKp46) was observed in NK cells in elderly individuals. KIR expression was increased only in the CD56(bright) subset. Children presented similar results regarding expression of NKp30 and KIR, but not NKp46. NKG2D expression was decreased in T cells of elderly subjects. Analysis of KIR genotype revealed that KIR2DL5 and KIR2DS3 were significantly associated with old age. Cytotoxic activity was preserved from childhood through old age, suggesting that the increase of the absolute number of CD56(dim), observed in elderly, may represent a compensatory mechanism for the receptor expression alterations. This initial study provides the framework for more focused studies of this subject, which are necessary to determine whether the changing balance of NK receptor expression may influence susceptibility to infectious, inflammatory, and neoplastic diseases.
Assuntos
Envelhecimento/imunologia , Células Matadoras Naturais/imunologia , Receptores de Células Matadoras Naturais/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Antígeno CD56/imunologia , Antígeno CD56/metabolismo , Criança , Pré-Escolar , Feminino , Genótipo , Antígenos HLA/genética , Humanos , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores de Células Matadoras Naturais/genética , Linfócitos T/imunologia , Linfócitos T/metabolismo , Adulto JovemRESUMO
Hematopoietic stem cells (HSC) can be identified by the expression of the CD34 molecule. CD34+ cells are found in bone marrow (BM), umbilical cord blood (UCB) and in mobilized peripheral blood (PB). CD34+ cells express P-glycoprotein (Pgp), a product of the multidrug resistance (MDR) gene. Pgp activity can be measured by the efflux of the dye Rhodamine 123 (Rho 123) and can be blocked by verapamil. Transport activity in HSC suggests that Pgp could have a functional role in stem cell differentiation. This study compared the number of CD34+ cells with Pgp activity measured by efflux of Rho 123 in the hematopoietic population obtained from different sources. Samples were analysed for their content of CD34+ cells, and BM had a significantly higher amount of CD34+ cells compared to UCB, mobilized PB and normal PB. When the frequency of Rholow cells was studied among the CD34+ population, an enrichment of cells with Pgp activity was observed. The frequency in BM was significantly lower than that in UCB and mobilized PB. The low retention of Rho 123 could be modified by verapamil, indicating that the measurements reflected dye efflux due to Pgp activity. Although UCB and mobilized PB had a lower number of CD34+ cells compared to BM, the total number of CD34+ cells with Pgp activity was similar in the three tissues. The different profiles may indicate the existence of subpopulations of stem cells or different stages of cellular differentiation detected by the extrusion of the dye Rho 123.
Assuntos
Antígenos CD34/metabolismo , Células da Medula Óssea/metabolismo , Sangue Fetal/metabolismo , Corantes Fluorescentes/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Rodamina 123/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Biomarcadores/metabolismo , Células da Medula Óssea/citologia , Diferenciação Celular , Separação Celular , Sangue Fetal/citologia , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Humanos , ImunofenotipagemAssuntos
Linfócitos T CD4-Positivos/química , Linfócitos T CD4-Positivos/patologia , Imunofenotipagem , Leucemia de Células T/diagnóstico , Leucemia de Células T/genética , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Idoso , Linfócitos T CD4-Positivos/metabolismo , Humanos , Imunofenotipagem/métodos , Leucemia de Células T/patologia , Linfoma de Células T/patologia , Masculino , Subpopulações de Linfócitos T/química , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologiaRESUMO
Estudou-se a reconstituição imunológica após transplante de medula óssea (TMO) em doenças malignas e não malignas. Em pacientes com anemia aplástica severa (AAS) s síndrome de Chédiak-Higashi, o TMO reverteu o defeito imunológico. Entretanto, foram detectadas diferenças na reconstituição entre pacientes com AAS e pacientes com leucemias, que podem ter resultado do tratamento prévio ou das drogas utilizadas no TMO, como o etoposídeo, que afetou a atividade NK. Mesmo nas leucemias, a recuperação não foi homogênea, pois indivíduos com leucemia mielóide crônica tiveram maior dificuldade em refazer seu comportamento de células T. O TMO não reviveu a ontogenia do sistema imune, pois os linfócitos apresentaram fenótipo de memória/ativado logo após o TMO. Detectaram-se diferenças dependentes do tipo de célula infundida, havendo uma reconstituição mais eficiente do compartimento de células B quando usadas células do sangue de cordão umbilical. Finalmente, não foi encontrado um padrão contra a população celular do inóculo e a incidência da doença enxerto contra hospedeiro.
Immunological recovery following bone marrow transplantation (BMT) was studied on malignant and non-malignant diseases. Patients suffering from severe aplastic anaemia (SAA) and Chédiak-Higashi syndrome had their immunological defects reverted by BMT. However, differences with regard to recovery were detected between patients with SAA and leukaemias. Furthermore, with regard to recovery the different leukaemias were not homogeneous. Patients with chronic myeloid leukaemia showed deficiencies in their T cell compartment. The differences observed might have resulted from previous anti-leukaemia treatment or from drugs utilised during BMT such as etopopside that affected NK activity. It was not possible to confirm that immunological recovery post BMT mimics the normal ontogeny as, soon after transplantation, lymphocytes presented the memory/activated phenotype. Differences dependent on the source of cells used for transplantation were also observed with a more efficient reconstitution of the B cell compartment when blood cells from the umbilical cord were infused. Finally, it was not possible to attribute the induction of grafi-versus-host disease to a particular cell population present in the inoculum.