RESUMEN
The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.
Asunto(s)
Neoplasias de Cabeza y Cuello/genética , Células Madre Hematopoyéticas/patología , Microambiente Tumoral/genética , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Médula Ósea/patología , Línea Celular Tumoral , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/patología , Humanos , RatonesRESUMEN
Tracheobronchial injuries are rare among all age groups and are extremely rare among the pediatric age group. Yet, the incidence has seemed to increase. Most of these patients die before reaching the hospital from severe associated injuries. Isolated bronchial injury is even more rare than tracheal injury, and it is the focus of the present study. A retrospective national survey was conducted among all tertiary referral and trauma centers in Israel regarding the period between the years 1983 and 1998. Only six cases (3 males and 3 females) of isolated bronchial rupture were found the throughout the country. Ages of the patients ranged from 2 to 14 years; all were involved in motor vehicle accidents, four of them as pedestrians. Ruptures occurred in the bronchus intermedicus (2 cases), left and right main bronchus (2 cases each). All but one patient went through primary repair. We give a full description of the procedure and discuss the literature regarding incidence, diagnosis, treatment, and outcome.
Asunto(s)
Bronquios/lesiones , Accidentes de Tránsito , Adolescente , Bronquios/cirugía , Broncografía , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Retrospectivos , Rotura , Tomografía Computarizada por Rayos X , Heridas y Lesiones/fisiopatologíaRESUMEN
Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila c-myc mutants, which are smaller as a result of hypotrophy. We find that c-myc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.
Asunto(s)
Genes cdc , Genes myc/fisiología , Linfocitos T/citología , Animales , Constitución Corporal/genética , Recuento de Células , Ciclo Celular/fisiología , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiología , División Celular/fisiología , Tamaño de la Célula , Células Cultivadas , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Drosophila , Embrión de Mamíferos/citología , Embrión no Mamífero , Fibroblastos , Marcación de Gen , Ratones , Proto-Oncogenes Mas , Especificidad de la Especie , Linfocitos T/inmunología , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/fisiologíaRESUMEN
Retrovirus-based vectors provide an efficient means to introduce and express genes in cells of the immune system and have become a popular tool to study immune function. They are easy to manipulate and provide stable, long-term gene expression because they integrate into the genome. Current retroviral vectors do have limitations that affect their usefulness in certain applications. However, recent advances suggest a number of ways in which these vectors might be improved to extend their utility in immunological research.
Asunto(s)
Vectores Genéticos , Retroviridae/genética , Retroviridae/inmunología , Animales , Expresión Génica , Marcadores Genéticos , Genoma Viral , Humanos , Regiones Promotoras Genéticas , Retroviridae/crecimiento & desarrollo , Retroviridae/patogenicidad , Transducción Genética , Virulencia/genéticaRESUMEN
The human immunodeficiency virus (HIV)-1 envelope glycoprotein is synthesized as a precursor (gp160) and subsequently cleaved to generate the external gp120 and transmembrane gp41 glycoproteins. Both gp120 and gp41 have been demonstrated to mediate critical functions of HIV, including viral attachment and fusion with the cell membrane. The antigenic variability of the HIV-1 envelope glycoprotein has presented a significant problem in the design of appropriate and successful vaccines and offers one explanation for the ability of HIV to evade immune surveillance. Therefore, the development and characterization of functional antibodies against conserved regions of the envelope glycoprotein is needed. Because of this need, we generated a panel of murine monoclonal antibodies (MuMabs) against the HIV-1 envelope glycoprotein. To accomplish this, we immunized Balb/C mice with a recombinant glycoprotein 160 (gp160) that was synthesized in a baculovirus expression system. From the growth-positive hybridomas, three MuMabs were generated that demonstrated significant reactivity with recombinant gp120 but failed to show reactivity against HIV-1 gp41, as determined by enzyme-linked immunosorbent assay (ELISA). Using vaccinia constructs that synthesize variant truncated subunits of gp160, we were able to map reactivity of all three of the Mabs (ID6, AC4, and AD3) to the first 204 residues of gp120 (i.e., the N terminus of gp120) via Western blot analysis. Elucidation of the epitopes for these Mabs may have important implications for inhibition of infection by HIV-1. Our initial attempts to map these Mabs with linear epitopes have not elucidated a specific antigenic determinant; however, several physical characteristics have been determined that suggest a continuous surface epitope. Although these antibodies failed to neutralize cell-free or cell-associated infection by HIV-1, they did mediate significant antibody-dependent cellular cytotoxicity (ADCC) activity, indicating potential therapeutic utility. In summary, these data suggest the identification of a potentially novel site in the first 200 aa of gp120 that mediates ADCC.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Epítopos/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Secuencia de Aminoácidos , Animales , Citotoxicidad Celular Dependiente de Anticuerpos , Ensayo de Inmunoadsorción Enzimática , Mapeo Epitopo , Proteína gp120 de Envoltorio del VIH/química , Humanos , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Pruebas de PrecipitinaRESUMEN
Transgenic mice have been used to explore the role of chromosomal translocations in the genesis of tumors. But none of these efforts has actually involved induction of a translocation in vivo. Here we report the use of Cre recombinase to replicate in vivo the t(8;21) translocation found in human acute myeloid leukemia (AML). As in the human tumors, the murine translocation fuses the genes AML1 and ETO. We used homologous recombination to place loxP sites at loci that were syntenic with the break points for the human translocation. Cre activity was provided in mice by a transgene under the control of the Nestin promoter, or in cultured B cells by infecting with a retroviral vector encoding Cre. In both instances, Cre activity mediated interchromosomal translocations that fused the AML1 and ETO genes. Thus, reciprocal chromosomal translocations that closely resemble rearrangements found in human cancers can be achieved in mice.
Asunto(s)
Proteínas de Unión al ADN/genética , Integrasas/metabolismo , Proteínas del Tejido Nervioso , Proteínas de Fusión Oncogénica/genética , Proteínas Proto-Oncogénicas , Factores de Transcripción/genética , Translocación Genética/genética , Proteínas Virales , Animales , Linfocitos B/fisiología , Secuencia de Bases , Células Cultivadas , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Modelos Animales de Enfermedad , Genes Reporteros/genética , Ingeniería Genética , Humanos , Integrasas/genética , Proteínas de Filamentos Intermediarios/genética , Leucemia Mieloide Aguda/genética , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Nestina , Proteínas de Fusión Oncogénica/metabolismo , Reacción en Cadena de la Polimerasa , Proteína 1 Compañera de Translocación de RUNX1 , Proteínas Recombinantes de Fusión/metabolismo , Retroviridae/genética , Retroviridae/metabolismo , Factores de Transcripción/metabolismo , Transgenes/genéticaRESUMEN
IL-2 is an important growth and survival factor for T lymphocytes but also sensitizes these cells to Fas-mediated activation-induced cell death (AICD). The molecular basis of these different effects of IL-2 was studied by introducing wild-type and mutant forms of the IL-2 receptor beta (IL-2Rbeta) chain that lacked specific signaling capacities into receptor-deficient T cells by retroviral gene transfer. Activation of Stat5 by IL-2 was found to be involved in T cell proliferation and promoted Fas ligand (FasL) expression and AICD. T cell survival was dependent on a receptor region that activated Akt and the expression of Bcl-2. Thus, distinct IL-2Rbeta chain signaling modules regulate T cell fate by stimulating growth and survival or by promoting apoptosis.
Asunto(s)
Apoptosis/inmunología , Interleucina-2/inmunología , Transducción de Señal/inmunología , Linfocitos T/inmunología , Receptor fas/inmunología , Animales , División Celular , Supervivencia Celular , Células Cultivadas , Proteína Ligando Fas , Técnicas de Transferencia de Gen , Vectores Genéticos , Humanos , Interleucina-2/farmacología , Activación de Linfocitos , Glicoproteínas de Membrana/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutagénesis , Receptores de Interleucina-2/genética , Retroviridae , Linfocitos T/citología , Linfocitos T/efectos de los fármacosRESUMEN
Apoptosis is a critical mechanism for regulating cell numbers during development, normal responses to hormones and other stimuli, and immune and inflammatory reactions. Recent advances in defining the biochemical mechanisms of cell death, and the development of animal models with isolated defects in cell death pathways, have led to an increasing appreciation of the pathophysiologic importance of lymphocyte apoptosis. In this article, we review our current understanding of the pathways and roles of apoptosis in lymphocytes, with an emphasis on transgenic and knockout models. We also summarize the relevance of these animal models to human diseases.
Asunto(s)
Apoptosis/genética , Apoptosis/inmunología , Linfocitos/citología , Linfocitos/inmunología , Modelos Genéticos , Animales , Autoinmunidad/genética , Humanos , Interleucina-2/genética , Activación de Linfocitos/genética , Ratones , Ratones Noqueados , Ratones Transgénicos , Proto-Oncogenes , Receptores de Interleucina-2/genética , Receptor fas/genéticaRESUMEN
The induction of apoptosis by death receptors serves to regulate immune responses by eliminating unwanted and harmful cells. Mature lymphocytes express FLICE inhibitory proteins (FLIPs) that block death receptor-induced cell death. Here, we show that both B and T cells downregulate c-FLIP upon activation in vitro. Retrovirus-mediated expression of c-FLIP blocks Fas-induced apoptosis of activated lymphocytes but does not affect cell death resulting from cytokine withdrawal. In vivo, c-FLIP expression results in defective superantigen-mediated elimination of T cells, the accumulation of activated B cells, the production of autoantibodies, and the development of autoimmune disease. No effect was seen on negative selection of thyomocytes. These results suggest that activation-dependent downregulation of c-FLIP renders mature lymphocytes sensitive to death receptor-mediated apoptosis and is required to maintain self-tolerance.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Autoinmunidad/inmunología , Linfocitos B/inmunología , Proteínas Portadoras/inmunología , Péptidos y Proteínas de Señalización Intracelular , Linfocitos T/inmunología , Animales , Apoptosis , Enfermedades Autoinmunes/inmunología , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Proteínas Portadoras/biosíntesis , Proteínas Portadoras/genética , Células Cultivadas , Regulación hacia Abajo , Enterotoxinas/inmunología , Proteína de Dominio de Muerte Asociada a Fas , Expresión Génica , Vectores Genéticos/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Retroviridae/genética , Staphylococcus aureus/inmunología , Superantígenos/inmunología , Receptor fas/inmunologíaRESUMEN
Activation-induced apoptosis of T lymphocytes is an important mechanism for maintaining self-tolerance. The sensitivity of T cells to apoptosis by the Fas pathway is regulated by the exposure of these cells to different cytokines. IL-2 is a survival and growth factor for T cells, as well as a necessary potentiator of Fas-mediated cell death. The role of this cytokine in triggering death pathways is the likely explanation for the autoimmune disease that develops as a result of targeted disruption of the IL-2 or IL-2 receptor alpha or beta chain gene.
Asunto(s)
Enfermedades Autoinmunes/inmunología , Citocinas/fisiología , AnimalesRESUMEN
Activation-induced cell death (AICD) of lymphocytes is an important mechanism of self-tolerance. In CD4+ T cells, AICD is mediated by the Fas pathway and is enhanced by IL-2. To define the mechanisms of this pro-apoptotic action of IL-2, we analyzed CD4+ T cells from wild-type and IL-2-/- mice expressing a transgenic T cell receptor. T cells become sensitive to AICD after activation by antigen and IL-2. IL-2 increases transcription and surface expression of Fas ligand (FasL) and suppresses transcription and expression of FLIP, the inhibitor of apoptosis. The ability of IL-2 to enhance expression of a pro-apoptotic molecule, FasL, and to suppress an inhibitor of Fas signaling, FLIP, likely accounts for the role of this cytokine in potentiating T cell apoptosis.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Apoptosis/inmunología , Linfocitos T CD4-Positivos/inmunología , Interleucina-2/fisiología , Péptidos y Proteínas de Señalización Intracelular , Receptor fas/inmunología , Animales , Antígenos de Superficie/inmunología , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Proteína Ligando Fas , Proteína de Dominio de Muerte Asociada a Fas , Tolerancia Inmunológica , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/inmunología , Ratones , Activación TranscripcionalRESUMEN
Novel approaches for the generation of more effective vaccines for HIV-1 are of significant importance. In this report we analyze the immunogenicity and efficacy of an HIV-1 DNA vaccine encoding env, rev and gag/pol in a chimpanzee model system. The immunized animals developed specific cellular and humoral immune responses. Animals were challenged with a heterologous chimpanzee titered stock of HIV-1 SF2 virus and followed for 48 weeks after challenge. Polymerase chain reaction coupled with reverse transcription (RT-PCR) results indicated infection in the control animal, whereas those animals vaccinated with the DNA constructs were protected from the establishment of infection. These studies serve as an important benchmark for the use of DNA vaccine technology for the production of protective immune responses.
Asunto(s)
Vacunas contra el SIDA/uso terapéutico , Infecciones por VIH/prevención & control , VIH-1/inmunología , Vacunas de ADN/uso terapéutico , Animales , Antígenos CD28/sangre , ADN Viral/análisis , Femenino , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/inmunología , Leucocitos Mononucleares/inmunología , Ganglios Linfáticos/virología , Masculino , Pruebas de Neutralización , Pan troglodytes , Linfocitos T Citotóxicos/inmunología , Vacunación , Carga ViralRESUMEN
The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 15-kDa virion-associated protein that functions as a regulator of cellular processes linked to the HIV life cycle. We report the interaction of a 41-kDa cytosolic viral protein R interacting protein 1 (Rip-1) with Vpr in vitro. Rip-1 displays a wide tissue distribution, including relevant targets of HIV infection. Vpr protein induced nuclear translocation of Rip-1, as did glucocorticoid receptor (GR)-II-stimulating steroids. Importantly, Vpr and Rip-1 coimmunoprecipitated with the human GR as part of an activated receptor complex. Vpr complementation of a vpr mutant virus was also mimicked by GR-II-stimulating steroids. Vpr and GR-II actions were inhibited by mifepristone, a GR-II pathway inhibitor. Together these data directly link the activity of the vpr gene product to the glucocorticoid steroid pathway and provide a biochemical mechanism for the cellular and viral activity of Vpr, as well as suggest that a unique class of antivirals, which includes mifepristone (RU486), may influence HIV-1 replication.
Asunto(s)
Productos del Gen vpr/metabolismo , VIH-1/metabolismo , Receptores de Glucocorticoides/metabolismo , Transcripción Genética , Proteínas Virales/metabolismo , Antivirales/farmacología , Transporte Biológico/efectos de los fármacos , Línea Celular , Núcleo Celular/metabolismo , Reactivos de Enlaces Cruzados , Dexametasona/farmacología , Productos del Gen vpr/genética , Prueba de Complementación Genética , VIH-1/genética , Humanos , Hidrocortisona/farmacología , Ligandos , Mifepristona/farmacología , Mutación , Pruebas de Precipitina , Unión Proteica , Proteínas Virales/aislamiento & purificación , Productos del Gen vpr del Virus de la Inmunodeficiencia HumanaRESUMEN
The vpr gene product of human immunodeficiency virus (HIV) and simian immunodeficiency virus is a virion-associated regulatory protein that has been shown using vpr mutant viruses to increase virus replication, particularly in monocytes/macrophages. We have previously shown that vpr can directly inhibit cell proliferation and induce cell differentiation, events linked to the control of HIV replication, and also that the replication of a vpr mutant but not that of wild-type HIV type 1 (HIV-1) was compatible with cellular proliferation (D. N. Levy, L. S. Fernandes, W. V. Williams, and D. B. Weiner, Cell 72:541-550, 1993). Here we show that purified recombinant Vpr protein, in concentrations of < 100 pg/ml to 100 ng/ml, increases wild-type HIV-1 replication in newly infected transformed cell lines via a long-lasting increase in cellular permissiveness to HIV replication. The activity of extracellular Vpr protein could be completely inhibited by anti-Vpr antibodies. Extracellular Vpr also induced efficient HIV-1 replication in newly infected resting peripheral blood mononuclear cells. Extracellular Vpr transcomplemented a vpr mutant virus which was deficient in replication in promonocytic cells, restoring full replication competence. In addition, extracellular Vpr reactivated HIV-1 expression in five latently infected cell lines of T-cell, B-cell, and promonocytic origin which normally express very low levels of HIV RNA and protein, indicating an activation of translational or pretranslational events in the virus life cycle. Together, these results describe a novel pathway governing HIV replication and a potential target for the development of anti-HIV therapeutics.
Asunto(s)
Productos del Gen vpr/fisiología , VIH-1/fisiología , Activación Viral , Latencia del Virus , Replicación Viral , Secuencia de Aminoácidos , Animales , Células Cultivadas , Datos de Secuencia Molecular , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/farmacología , Productos del Gen vpr del Virus de la Inmunodeficiencia HumanaRESUMEN
In human immunodeficiency virus (HIV)-positive individuals, the vast majority of infected peripheral blood cells and lymph node cells may be latently or nonproductively infected. The vpr open reading frame of HIV-1 encodes a 15-kDa virion-associated protein, Vpr. The vpr gene has been shown to increase virus replication in T cells and monocyte/macrophages in vitro. We have previously reported that vpr expression in various tumor lines leads to growth inhibition and differentiation, indicating that Vpr may function as a regulator of cellular permissiveness to HIV replication. Here we show that Vpr protein is present in significant amounts in the serum of AIDS patients. Purified serum Vpr activated virus expression from five latently infected cell lines, U1, OM.10.1, ACH-2, J1.1, and LL58. Serum Vpr also activated virus expression from resting peripheral blood mononuclear cells of HIV-infected individuals. Together, these findings implicate serum Vpr in the activation of HIV replication in vivo and in the control of latency. Anti-Vpr antibodies inhibited Vpr activity, suggesting that humoral immunity modulates Vpr activity in vivo. These results have broad implications for the virus life cycle and for the prospective control of HIV replication and pathogenesis.
Asunto(s)
Productos del Gen vpr/fisiología , Infecciones por VIH/microbiología , VIH-1/crecimiento & desarrollo , Replicación Viral , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/líquido cefalorraquídeo , Síndrome de Inmunodeficiencia Adquirida/microbiología , Secuencia de Aminoácidos , Productos del Gen vpr/sangre , Productos del Gen vpr/líquido cefalorraquídeo , Infecciones por VIH/sangre , Infecciones por VIH/líquido cefalorraquídeo , Humanos , Datos de Secuencia Molecular , Péptidos/química , Productos del Gen vpr del Virus de la Inmunodeficiencia HumanaRESUMEN
Recently, immunization techniques in which DNA constructs are introduced directly into mammalian tissue in vivo have been developed. In theory, gene inoculation should result in the production of antigenic proteins in a natural form in the immunized host. Here we present the use of such a technique for the inoculation of mice with a human immunodeficiency virus type 1 (HIV-1) envelope DNA construct (pM160). Mice were injected intramuscularly with pM160 and were subsequently analyzed for their anti-HIV envelope immune responses. Antisera collected from inoculated animals reacted with the recombinant HIV-1 envelope in ELISA and immunoprecipitation assays. The antisera also contained antibodies that were able to neutralize HIV-1 infection and inhibit HIV-1-mediated syncytium formation in vitro. Furthermore, splenic lymphocytes derived from pM160-inoculated animals demonstrated HIV-envelope-specific proliferative responses. The gene inoculation technique mimics features of vaccination with live attenuated viruses and, therefore, may ultimately prove useful in the rapid development of safe and efficacious vaccines as it provides for production of relevant antigen in vivo without the use of infectious agents.
Asunto(s)
Formación de Anticuerpos , Productos del Gen env/inmunología , VIH-1/inmunología , Inmunidad Celular , Precursores de Proteínas/inmunología , Transfección/inmunología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Antígenos CD4/metabolismo , Línea Celular , Clonación Molecular , Ensayo de Inmunoadsorción Enzimática , Productos del Gen env/administración & dosificación , Productos del Gen env/genética , Genes rev , Genes tat , Proteínas gp160 de Envoltorio del VIH , VIH-1/genética , VIH-1/fisiología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C/inmunología , Datos de Secuencia Molecular , Músculos/fisiología , Pruebas de Neutralización , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa/métodos , Precursores de Proteínas/administración & dosificación , Precursores de Proteínas/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunologíaRESUMEN
The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies.