RESUMEN
Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT.
Asunto(s)
Aspergilosis , Aspergillus , Candida , Candidiasis , Trasplante de Células Madre de Sangre del Cordón Umbilical , Neoplasias Hematológicas , Sistema de Registros , Adolescente , Adulto , Anciano , Aloinjertos , Aspergilosis/etiología , Aspergilosis/mortalidad , Aspergilosis/terapia , Candidiasis/etiología , Candidiasis/mortalidad , Candidiasis/terapia , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Lactante , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
It is unclear whether blood culture samples should be obtained through one or multiple catheter lumens. We measured how frequently drawing blood cultures from all the lumens from a multilumen catheter resulted in discordant results and how often these caused medical interventions. We performed a retrospective review of the microbiology database of the National Institutes of Health (NIH) Clinical Center. Most patients were immunocompromised. All blood cultures obtained from May 1, 2007 to April 30, 2009 were reviewed. We analyzed all positive blood cultures (i.e., positivity of any of the blood cultures drawn through the catheter lumens) when simultaneous samples from different lumens were obtained, and reviewed the medical charts of those in which blood cultures from different lumens had discordant results (i.e., not all lumens revealed the same organism). We also analyzed how often the discordant results lead to a medical intervention, defined as a change of antimicrobials and/or removal of the catheter. There were 405 episodes of positive blood cultures, in which simultaneous samples of different lumens of a multilumen catheter were obtained. Eighty-five episodes (21 %) were considered to be contaminants and excluded. We analyzed 320 episodes of positive blood cultures in 153 patients; 173 episodes (54.1 %) had discordant results. In 77 % of the 173 episodes, the discordant isolate led to a medical intervention. In immunocompromised patients, sampling all the lumens of a multilumen catheter results in more positive blood cultures, and many of these result in medical interventions. When evaluating bloodstream infection in patients with multilumen catheters, sampling all lumens should be strongly considered.
Asunto(s)
Recolección de Muestras de Sangre/métodos , Sangre/microbiología , Catéteres/microbiología , Técnicas Microbiológicas/métodos , Sepsis/diagnóstico , Sepsis/microbiología , Humanos , Estudios RetrospectivosRESUMEN
A 38-year-old female patient with systemic lupus erythematosus presented with pulmonary infiltrates and hypoxemia for several months following immunodepleting autologous hematopoietic stem cell transplantation. She was treated for influenza, which was isolated repeatedly from oropharynx and bronchoalveolar lavage (BAL) fluids, and later empirically for lupus pneumonitis, but died 6 months after transplant. Autopsy findings failed to show influenza in the lungs or lupus pneumonitis. A novel generic polymerase chain reaction (PCR)-based assay using degenerate primers identified human coronavirus (CoV) HKU1 RNA in BAL fluid at autopsy. CoV was confirmed by virus-specific PCRs of lung tissue at autopsy. Electron microscopy showed viral particles consistent with CoV HKU1 in lung tissue both at autopsy and from a previous biopsy. Although human CoV HKU1 infection is not usually severe, in highly immunocompromised patients, it can be associated with fatal pneumonia.
Asunto(s)
Infecciones por Coronavirus/virología , Coronavirus/clasificación , Coronavirus/aislamiento & purificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Pulmón/virología , Neumonía Viral/virología , Adulto , Autopsia , Biopsia , Coronavirus/genética , Infecciones por Coronavirus/diagnóstico , Resultado Fatal , Femenino , Humanos , Neumonía Viral/diagnóstico , Reacción en Cadena de la Polimerasa/métodosRESUMEN
We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Micosis/diagnóstico , Volvariella/aislamiento & purificación , Adulto , Biopsia , Encéfalo/diagnóstico por imagen , Encéfalo/patología , ADN de Hongos/química , ADN de Hongos/genética , ADN Ribosómico/química , ADN Ribosómico/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Resultado Fatal , Femenino , Genes de ARNr , Histocitoquímica , Humanos , Imagen por Resonancia Magnética , Microscopía , Datos de Secuencia Molecular , Micosis/microbiología , ARN Ribosómico 5.8S/genética , Radiografía Torácica , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: A graft-versus-lymphoma effect against diffuse large B-cell lymphoma (DLBCL) is inferred by sustained relapse-free survival after allogeneic stem-cell transplantation; however, there are limited data on a direct graft-versus-lymphoma effect against DLBCL following immunotherapeutic intervention by either withdrawal of immunosuppression or donor lymphocyte infusion (DLI). MATERIALS AND METHODS: An analysis was carried out to determine whether a direct graft-versus-lymphoma effect exists against DLBCL. The analysis was restricted to patients with DLBCL, who were either not in complete remission at day +100 after allogeneic stem-cell transplantation or subsequently relapsed beyond this time point. RESULTS: Fifteen patients were identified as either not in complete remission (n = 13) at their day +100 evaluation or subsequently relapsed (n = 2) and were assessed for subsequent responses after withdrawal of immunosuppression or DLI. Eleven patients were treated with either withdrawal of immunosuppression (n = 10) or a DLI (n = 1) alone; four patients received chemotherapy with DLI to reduce tumor bulk. Nine (60%) patients subsequently responded (complete = 8, partial = 1). Six responses occurred after withdrawal of immunosuppression alone. Six patients are alive (range 42-83+ months) in complete remission without further treatment. CONCLUSION: The demonstration of sustained complete remission following immunotherapeutic intervention provides direct evidence of a graft-versus-lymphoma effect against DLBCL.
Asunto(s)
Efecto Injerto vs Tumor/inmunología , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The transmission spectrum of three-level atoms in a vapor cell inside an optical cavity shows distinct peaks associated with atom-cavity polaritons in the system. We develop the theory of these resonances in a Doppler-broadened medium and present the results of experimental observations of these spectra in three-level Lambda-type rubidium atoms inside an optical ring cavity.
Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Ganciclovir/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Reacción en Cadena de la Polimerasa/normas , Quimioprevención , Infecciones por Citomegalovirus/sangre , ADN Viral/análisis , Reacción en Cadena de la Polimerasa/métodos , Guías de Práctica Clínica como Asunto/normas , Valores de Referencia , Trasplante HomólogoRESUMEN
We investigate steady state entanglement in an open quantum system, specifically a single atom in a driven optical cavity with cavity loss and spontaneous emission. The system reaches a steady pure state when driven very weakly. Under these conditions, there is an optimal value for atom-field coupling to maximize entanglement, as larger coupling favors a loss port due to the cavity enhanced spontaneous emission. We address ways to implement measurements of the entanglement and find that normalized cross-correlation functions are indicators of the entanglement in the system. The equal time intensity-field cross correlation between the transmitted field of the cavity and the fluorescence intensity is proportional to the entanglement of formation for weak driving fields.
RESUMEN
For an atom in an externally driven cavity, we show that special initial states lead to near-disentangled atom-field evolution, and superpositions of these can lead to near maximally entangled states. Somewhat counterintutively, we find that (moderate) spontaneous emission in this system actually leads to a transient increase in entanglement beyond the steady-state value. We also show that a particular field correlation function could be used, in an experimental setting, to track the time evolution of this entanglement.
RESUMEN
Expression of the alpha chain of the interleukin 2 receptor on T lymphocytes is restricted, increasing in the setting of activation, particularly after antigenic stimulation via the TCR. The effects of IL-2 in vitro on the expression of CD25 and proliferation as well as the cytokine induction in CD25-depleted T cells were studied. CD25-depleted and PBMC of healthy donors were cultured for 7 days with 0, 10, or 100 IU/ml of IL-2. Phenotypic analysis and measurement of cytokines in the culture supernatants were performed. IL-2 led to a dose-dependent induction of the IL-2R alpha chain on both CD4 and CD8 T lymphocytes. In the CD25-depleted cultures, IL-2 treatment (100 IU/ml) increased the percentage of CD4 T cells expressing CD25 by 30.6% (P = 0.05) and of CD8 T cells by 48.2% (P = 0.01) on day 7 compared to no treatment. In the PBMC cultures the increase on day 7 was 36.4% for CD4 (P = 0.01) and 50.8% (P = 0.025) for CD8 T lymphocytes. The patterns of cytokine induction in the CD25-depleted and control cultures were similar with increases of IFN-gamma, GM-CSF, IL-16, TNF alpha, and soluble IL-2 receptor in the IL-2-containing cultures. CFSE experiments demonstrated the proliferative capacity of both CD25-positive and -negative T cells. Interleukin 2 alone can lead to a dose-dependent induction of the alpha chain of its receptor on resting CD4 and CD8 T lymphocytes. IL-2 as a sole stimulant is also associated with generation of a cytokine milieu that includes IFN-gamma, GM-CSF, IL-16, and TNF alpha.
Asunto(s)
Interleucina-2/farmacología , Receptores de Antígenos de Linfocitos T alfa-beta/fisiología , Receptores de Interleucina-2/análisis , Linfocitos T/inmunología , Muerte Celular/efectos de los fármacos , Citocinas/sangre , Relación Dosis-Respuesta Inmunológica , Humanos , Fenotipo , Receptores de Interleucina-2/fisiología , Linfocitos T/metabolismoRESUMEN
Although skewing of the CD4+ TCR repertoire in advanced HIV infection is well documented, increases in polyclonality during antiretroviral therapy have been less consistently observed. Ten patients, each with documented abnormalities within the CD4+ TCR repertoire, were studied by CDR3 spectratyping, semiquantitative PCR, and SSCP during 9-26 months of therapy. Naive and memory cell phenotypes were analyzed by flow cytometry. Six of 10 patients showed increased polyclonality of their TCR repertoires, 1 showed no change, and 3 showed increased TCR skewing, despite suppressed viral replication. Overall, there was no significant change in the percentage of abnormal BV subfamilies (from a mean of 25.5 to 17.1%) or the percentage of naive CD4+ T cells (from a mean of 18 to 25%). Further, progression of TCR repertoire disruptions was observed in some patients even with suppression of plasma viral RNA below 500 copies/ml. Although a spectrum of changes may be seen within the CD4+ TCR repertoire in the setting of antiretroviral therapy, increases in polyclonality are observed in some patients.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Memoria Inmunológica , Receptores de Antígenos de Linfocitos T/genética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/clasificación , Linfocitos T CD4-Positivos/metabolismo , Regiones Determinantes de Complementariedad/metabolismo , Quimioterapia Combinada , Citometría de Flujo , Variación Genética/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Fenotipo , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Estudios Prospectivos , Receptores de Antígenos de Linfocitos T/metabolismo , Transcripción Genética , Replicación ViralRESUMEN
The virus-specific CD8+ T cell responses of 21 HIV-infected patients were studied including a unique cohort of long-term nonprogressors with low levels of plasma viral RNA and strong proliferative responses to HIV Ags. HIV-specific CD8+ T cell responses were studied by a combination of standard cytotoxic T cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular IFN-gamma in response to HIV-vaccinia recombinant-infected autologous B cells. Very high frequencies (0.8-18.0%) of circulating CD8+ T cells were found to be HIV specific. High frequencies of HIV-specific CD8+ T cells were not limited to long-term nonprogressors with restriction of plasma virus. No correlation was found between the frequency of HIV-specific CD8+ T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to gag-pol. Repertoire analysis showed these large numbers of Ag-specific cells were scattered throughout the repertoire and in the majority of cases not contained within large monoclonal expansions. These data demonstrate that high numbers of HIV-specific CD8+ T cells exist even in patients with high-level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8+ T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive disease.
Asunto(s)
Citotoxicidad Inmunológica , Epítopos de Linfocito T/inmunología , Antígenos VIH/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/virología , Adulto , Secuencia de Aminoácidos , Pruebas Inmunológicas de Citotoxicidad , Progresión de la Enfermedad , Epítopos de Linfocito T/análisis , Epítopos de Linfocito T/genética , Femenino , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Humanos , Interferón gamma/metabolismo , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Linfocitos T Citotóxicos/metabolismoRESUMEN
High levels of resistance to challenge with human immunodeficiency virus type 1 SF162 were observed in animals engrafted with peripheral blood mononuclear cells of four long-term nonprogressors (LTNPs). Resistance was abrogated by depletion of CD8(+) T cells in vivo and was observed only in LTNPs with proliferative responses to p24. In a subgroup of nonprogressors, CD8(+) T cells mediated restriction of challenge viruses, and this response was associated with strong proliferative responses to p24 antigen.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Proteína p24 del Núcleo del VIH/inmunología , Sobrevivientes de VIH a Largo Plazo , VIH-1/fisiología , Replicación Viral , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/virología , División Celular , Trasplante de Células , Progresión de la Enfermedad , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , VIH-1/inmunología , Humanos , Inmunidad Innata/inmunología , Leucocitos Mononucleares/trasplante , Leucocitos Mononucleares/virología , Masculino , Ratones , Ratones SCIDRESUMEN
The weight of the published evidence suggest that there is clinically significant immune recovery in a sizable fraction of HIV-infected patients who achieve suppression of viral replication. At the same time, it is clear that very few patients regain normal (i.e. equivalent to pre-infection) immune function, at least after the follow-up periods available so far. The experience from bone-marrow transplantation or intensive chemotherapy in adults suggests that such kind of immune reconstitution is unlikely (at least with treatments limited to stopping virus replication) once the immune system has been sufficiently damaged. It is also clear that effective immunity to HIV is not achieved in a significant proportion of patients. These findings have implications for both basic research and clinical practice. From the laboratory perspective, besides the urgent need to characterize the protective immunity to HIV (if it exists), it would be desirable to find some simple measure of the immune function of patients who receive therapy. The combination of markers of immune activation together with CD4 cell count and viral load should be further evaluated in this context. Regarding clinical practice, it is likely that prophylaxes for opportunistic infections can be discontinued uneventfully in the majority of patients responding to HAART. Although the evidence is not yet conclusive, all available data suggest this will be the case. Given that there is significant immune reconstitution even in advanced disease, it is tempting to consider if this fact can be used to support antiviral therapy recommendations that are less aggressive than the current ones. HIV eradication by pharmacologic means alone does not seem possible yet, and no effective immune response to HIV seems to be generated by starting therapy in the asymptomatic (as opposed to acute infection) stage of the disease. At the same time, the follow-up studies on prolonged antiretroviral therapy suggest that virologic failure will take place despite many months of seemingly adequate suppression. This fact, taken together with the side effects and inconvience of current antiretroviral regimens, can be used to support an argument in favor of evaluating strategies to treat later rather than earlier.
Asunto(s)
Infecciones por VIH/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos , Activación de LinfocitosRESUMEN
The immunodeficiency caused by human immunodeficiency virus (HIV) infection may be related to loss of diversity in the T cell receptor (TCR) repertoire. A cross-sectional study of the CD4 TCR repertoire was done for patients at various stages of HIV infection. Semiquantitative polymerase chain reaction was used to study the relative usage of the variable chain beta (BV) subfamilies and the size distributions of transcripts (CDR3 size analysis) within these subfamilies. The relative usage of the TCRBV subfamilies of patients and controls was not significantly different. The proportion of subfamilies with abnormal CDR3 size patterns was higher in the HIV-infected patients (25%, 95% confidence interval [CI], 17%-33%) than in the controls (7.2%, 95% CI, 2.3%-12.1%; P < .001), with a significant negative correlation between the number of CD4 cells and the percentage of abnormal TCRBV subfamilies. These results indicate that progressive loss of CD4 T cells is accompanied by increasing disruptions within the T cell receptor repertoire.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , Complejo Receptor-CD3 del Antígeno de Linfocito T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Recuento de Linfocito CD4 , Estudios Transversales , Humanos , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , Análisis de Secuencia de ADNRESUMEN
We investigated whether 2-chlorodexoyadenosine could induce apoptosis in B cell chronic lymphocytic leukemia (B-CLL) cells in vitro using clinically achievable drug doses, measuring apoptosis ratio by flow cytometry. B cells were isolated from previously untreated patients and apoptosis was measured in these cells immediately after isolation and following incubation in vitro, without and with 2-chlorodeoxyadenosine at different concentrations, for 24 and 48 h. Distribution of cellular DNA content and quantitative analysis of apoptosis were determined by standard propidium iodide staining and flow cytometry. Spontaneous apoptosis occurred in B-CLL cells incubated in vitro in the absence of drug, but the level of apoptosis was greater in cells treated with 2-chlorodeoxyadenosine after the second day of culture. The present in vitro study of B-CLL cells from previously untreated patients suggests this chemotherapeutic agent activates a program of cell death by apoptosis using a drug dose equivalent to the physiological concentration used in patients in vivo. These data reveal an interesting possibility in the 2-chlorodeoxyadenosine treatment of untreated patients by neoplastic B cell apoptosis induction.
Asunto(s)
Apoptosis/efectos de los fármacos , Cladribina/farmacología , Leucemia Linfocítica Crónica de Células B/patología , Adulto , Anciano , Fragmentación del ADN/efectos de los fármacos , ADN de Neoplasias/análisis , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Células Tumorales CultivadasRESUMEN
BACKGROUND: Although there are a number of reports concerned with the role of immunity in the sudden onset of progressive sensorineural hearing loss, there are few references dealing with the involvement of immune-mediated mechanisms in sudden deafness. OBJECTIVES: To study the phenotype of peripheral blood lymphocytes in a group of patients with sudden deafness by use of 3-color flow cytometry. DESIGN: The study was carried out prior to the start of steroid therapy. Fourteen patients underwent a follow-up study once steroid therapy had been completed. Prospective analysis, case-control. SETTING: Tertiary case referral center, ambulatory and hospitalized care. PATIENTS: Twenty-two patients (13 men and 9 women; mean age, 45.3 years) were compared with 14 healthy control subjects (9 men and 5 women; mean age, 36 years). Patients were divided in 2 groups according to their response to steroid therapy. RESULTS: Decreased numbers of both CD4+ helper cells (38.4% vs 45.5%; P = .04) and CD8+ cytotoxic cells (17.5% vs 22.3%; P = .02) were observed in patients and compared with those in the control subjects, as well as reduced numbers of CD4+CD45RA+ cells (14.4% vs 29.3%; P = .01) and CD8+CD45RA+ naive cells (18.2% vs 25.4%; P = .04). In the group of patients with a good response to steroid therapy (group 1), a tendency toward normalization of the CD4+ (pretreatment, 38.6%; posttreatment, 44.6%), CD4+CD45RA+ (pretreatment, 15.2%; posttreatment, 21.7%), and CD4+CD45RO+ (pretreatment, 21.1%; posttreatment, 18.2%) cell counts was observed, with a slight decrease in the CD8+ population (pretreatment, 18%; posttreatment, 15.7%). However, in patients with a poorer response (group 2), while there were increases in the CD4+ (pretreatment, 38%, posttreatment, 50%) and CD4+CD45RA+ (pretreatment, 12.8%; posttreatment, 16.7%) cell counts after steroid therapy, there was a significant increment in the CD4+CD45RO+ memory cell count (pretreatment, 14.1%; posttreatment, 28.5%) and low CD8+CD45RA+ counts (pretreatment, 14.6%; posttreatment, 15.5%). No differences were observed in the numbers of B or natural killer cells or in the presence of activation antigens CD25 and HLA-DR when pretreatment and posttreatment levels were compared. CONCLUSION: These results demonstrate significant abnormalities in the subpopulations of lymphocytes in patients with sudden hearing loss, suggesting the existence of immune-mediated responses in the inner ear as possible etiopathogenic factors in this entity.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Pérdida Auditiva Súbita/inmunología , Síndromes de Inmunodeficiencia/inmunología , Adolescente , Adulto , Enfermedades Autoinmunes/tratamiento farmacológico , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Estudios de Casos y Controles , Femenino , Citometría de Flujo/métodos , Glucocorticoides/uso terapéutico , Pérdida Auditiva Súbita/tratamiento farmacológico , Humanos , Síndromes de Inmunodeficiencia/tratamiento farmacológico , Inmunofenotipificación , Antígenos Comunes de Leucocito/efectos de los fármacos , Antígenos Comunes de Leucocito/inmunología , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Changes in CD4+ T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4+ T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4+ T cells increased only if they were present before initiation of therapy. Disruptions of the CD4+ TCR repertoire were most prevalent in patients with the lowest CD4+ T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4+ T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4+ T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4+ T cells and disruptions of the CD4+ T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies.