IL-7 is critical for homeostatic proliferation and survival of naïve T cells

In T cell-deficient conditions, naïve T cells undergo spontaneous “homeostatic” proliferation in response to contact with self-MHC/peptide ligands. With the aid of an in vitro system, we show here that homeostatic proliferation is also cytokine-dependent. The cytokines IL-4, IL-7, and IL-15 enhanced homeostatic proliferation of naïve T cells in vitro. Of these cytokines, only IL-7 was found to be critical; thus, naïve T cells underwent homeostatic proliferation in IL-4− and IL-15− hosts but proliferated minimally in IL-7− hosts. In addition to homeostatic proliferation, the prolonged survival of naïve T cells requires IL-7. Thus, naïve T cells disappeared gradually over a 1-month period upon adoptive transfer into IL-7− hosts. These findings indicate that naïve T cells depend on IL-7 for survival and homeostatic proliferation.

DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state.

Transgenic mice expressing the sequences coding for the envelope proteins of the hepatitis B virus (HBV) in the liver have been used as a model of the HBV chronic carrier state. We evaluated the possibility of inducing a specific immune response to the viral envelope antigens and thus potentially controlling chronic HBV infection. Using HBV-specific DNA-mediated immunization in this transgenic model, we show that the immune response induced after a single intramuscular injection of DNA resulted in the complete clearance of circulating hepatitis B surface antigen and in the long-term control of transgene expression in hepatocytes. This response does not involve a detectable cytopathic effect in the liver. Adoptive transfer of fractionated primed spleen cells from DNA-immunized mice shows that T cells are responsible for the down-regulation of HBV mRNA in the liver of transgenic mice. To our knowledge, this is the first demonstration of a potential immunotherapeutic application of DNA-mediated immunization against an infectious disease and raises the possibility of designing more effective ways of treating HBV chronic carriers.

The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product.

Tumors express peptide antigens capable of being recognized by tumor-specific cytotoxic T lymphocytes (CTL). Immunization of mice with a carcinogen-induced colorectal tumor, CT26, engineered to secrete granulocyte/macrophage colony-stimulating factor, routinely generated both short-term and long-term CTL lines that not only lysed the parental tumor in vitro, but also cured mice of established tumor following adoptive transfer in vivo. When either short-term or long-term CTL lines were used to screen peptides isolated from CT26, one reverse-phase high performance liquid chromatography peptide fraction consistently sensitized a surrogate target for specific lysis. The bioactivity remained localized within one fraction following multiple purification procedures, indicating that virtually all of the CT26-specific CTL recognized a single peptide. This result contrasts with other tumor systems, where multiple bioactive peptide fractions have been detected. The bioactive peptide was identified as a nonmutated nonamer derived from the envelope protein (gp70) of an endogenous ecotropic murine leukemia provirus. Adoptive transfer with CTL lines specific for this antigen demonstrated that this epitope represents a potent tumor rejection antigen. The selective expression of this antigen in multiple non-viral-induced tumors provides evidence for a unique class of shared immunodominant tumor associated antigens as targets for antitumor immunity.

Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23).

The observation that overt type I diabetes is often preceded by the appearance of insulin autoantibodies and the reports that prophylactic administration of insulin to biobreeding diabetes-prone (BB-DP) rats, nonobese diabetic (NOD) mice, and human subjects results in protection from diabetes suggest that an immune response to insulin is involved in the process of beta cell destruction. We have recently reported that islet-infiltrating cells isolated from NOD mice are enriched for insulin-specific T cells, that insulin-specific T cell clones are capable of adoptive transfer of diabetes, and that epitopes present on residues 9-23 of the B chain appear to be dominant in this spontaneous response. In the experiments described in this report, the epitope specificity of 312 independently isolated insulin-specific T cell clones was determined and B-(9-23) was found to be dominant, with 93% of the clones exhibiting specificity toward this peptide and the remainder to an epitope on residues 7-21 of the A chain. On the basis of these observations, the effect of either subcutaneous or intranasal administration of B-(9-23) on the incidence of diabetes in NOD mice was determined. The results presented here indicate that both subcutaneous and intranasal administration of B-(9-23) resulted in a marked delay in the onset and a decrease in the incidence of diabetes relative to mice given the control peptide, tetanus toxin-(830-843). This protective effect is associated with reduced T-cell proliferative response to B-(9-23) in B-(9-23)-treated mice.

T-cell receptor (TCR) usage in Lewis rat experimental autoimmune encephalomyelitis: TCR beta-chain-variable-region V beta 8.2-positive T cells are not essential for induction and course of disease.

Predominant usage of V beta 8.2 gene segments, encoding a T-cell receptor (TCR) beta chain variable region, has been reported for pathogenic Lewis rat T cells reactive to myelin basic protein (MBP). However, up to 75% of the alpha/beta T cells in a panel of MBP-specific T-cell lines did not display TCR V beta 8.2, V beta 8.5, V beta 10, or V beta 16 elements. To further investigate TCR usage, we sorted the T-cell lines for V beta 8.2- and V beta 10-positive T cells or depleted the lines of cells with these TCRs. V beta 8.2-positive T cells and one of the depleted T-cell lines strongly reacted against the MBP peptide MBP-(68-88). The depleted T-cell line caused marked experimental autoimmune encephalomyelitis (EAE) even in Lewis rats in which endogenous V beta 8.2-positive T cells had been eliminated by neonatal treatment with anti-V beta 8.2 monoclonal antibodies. T-cell hybridomas generated from this line predominantly used V beta 3 TCR genes coexpressed with TCR V alpha 2 transcripts, which were also used by V beta 8.2-positive T cells. Furthermore, V beta 10-positive T cells reactive to MBP-(44-67) were encephalitogenic when injected immediately after positive selection. After induction of EAE by sorted V beta 8.2- or V beta 10-positive T-cell lines, immunocytochemical analysis of the spinal cord tissue showed a predominance of the injected TCR or of nontypable alpha/beta T cells after injection of the depleted line. Our results demonstrate heterogeneity of TCR beta-chain usage even for a single autoantigen in an inbred strain. Moreover, V beta 8.2-positive T cells are not essential for the induction and progression of adoptive-transfer EAE.

Gay Couples Who Adopt Children Who Have Been Abused: Ideas and Interventions From a Self Psychological Perspective to Facilitate the Adoption Process

here are currently hundreds of thousands of children in the US foster care system who are all in need of a stable and predictable home with parents on whom they can depend. Recently, there has been an increased interest in adoption from gay couples who want to start a family. Because the majority of children in the foster care system have some sort of abuse or neglect history, a large number of them present with difficulties such as oppositional behavior, mood dysregulation, and other kinds of mental health problems. This paper addresses the unique situation of gay couples who adopt children who have been abused. Kohut's self psychology theory is utilized to help identify strengths and potential problems that could arise from this type of situation. Particular attention is given to the three selfobject needs that are central in self psychology: mirroring, idealization, and twinship. Additionally, ideas for interventions are posed for potential adoptive parents and mental health professionals to use to help the adoption process progress more smoothly and to hopefully lead to long-term, healthy placements.

Las encuestas autoadministradas por internet. Un estudio de caso: “las familias adoptivas y sus estilos de vida”

España se convierte, en 2004, en el segundo país del mundo en adopción internacional propiciando que la familia adoptiva adquiera una gran visibilidad y relevancia social. El artículo presenta los hallazgos obtenidos a partir de la administración online, a madres y padres adoptivos españoles, de la encuesta Web “Las familias adoptivas y sus estilos de vida”. En concreto, se exponen los resultados obtenidos sobre las actitudes, opiniones y percepción de la norma social en materia de adopción. Este análisis permite explorar los factores explicativos que determinan que un subconjunto de la población opte por la adopción al tiempo que nos acerca a la comprensión sociológica tanto del incremento de las adopciones en España como de las familias adoptivas. Adicionalmente, el artículo expone los aspectos técnicos relacionados con el diseño y aplicación de la encuesta on-line con el objetivo de evidenciar que, a pesar de las limitaciones propias de esta forma de aplicación, esta arrojar luz sobre el proceso de adopción internacional, escasamente explorado en la investigación sociológica española con encuestas.

Estigma social y adopción internacional en España. ¿Es la familia adoptiva un modelo familiar menos «auténtico» que los basados en lazos biológicos?

En España, el fenómeno de las adopciones internacionales irrumpe en la década de 1990. En 2004, se convirtió en el segundo país del mundo que las llevaba a cabo. Con el objetivo de incrementar el conocimiento sociológico sobre la familia adoptiva internacional española, se realizó la encuesta a través de web titulada Las familias adoptivas y sus estilos de vida. A partir de las respuestas ofrecidas por 230 madres y padres adoptivos, se dibuja el perfil sociodemográfico de sus hogares. Estos se caracterizarían por contar con progenitores con elevado nivel formativo, no adscritos a ninguna religión, que defienden políticas de izquierdas y que comparten un sistema de valores posmodernos respecto a la institución familiar. La identificación de la estructura doméstica según su tipo de alianza (biparental o monoparental) y su tipo de filiación (adoptiva o mixta) nos permite situar a la adopción contemporánea como una opción de filiación elegida y no, exclusivamente, como alternativa ante la imposibilidad de tener hijos biológicos. Adicionalmente, los resultados arrojados por la encuesta nos permiten adentrarnos en uno de los aspectos menos abordados en el estudio sociológico de la familia adoptiva: el papel de las actitudes sociales hacia la adopción y su impacto en aquella. La mayoría de los encuestados perciben el estigma social del que es objeto su familia adoptiva, pues, desde su punto de vista, la sociedad las considera como una forma de hogar menos satisfactoria que la basada en lazos biológicos.

«Somos iguales a cualquier otra familia… estamos convencidos de que somos verdaderos padres y de que formamos una auténtica familia». Las familias adoptivas en el catálogo de las nuevas formas familiares

En este artículo abordamos el significado de la familia adoptiva a partir del análisis del discurso de los relatos autobiográficos de madres y padres adoptivos españoles. En un contexto de vacío de cultura adoptiva, las familias adoptivas publican narraciones para ser valoradas como «normales» al tiempo que, en ausencia de modelos de referencia, definen su modelo de familia desdibujando el arquetipo familiar instituido. A partir del método biográfico, aplicamos un doble ejercicio sociológico de (1) deconstrucción ideológica del modelo de familia hegemónico a partir de la (2) construcción del significado que padres y madres adoptivas otorgan a su familia. Las teorías de la familia postmoderna y las teorías feministas postestructuralistas enmarcan el análisis crítico del discurso con perspectiva de género con el que es abordado el estudio de estos singulares documentos personales.

Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation

BACKGROUND Intravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). METHODS The clinical efficacy of IVIG and IVIG-derived F(ab')2 fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA. RESULTS We report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG-derived Fc fragments are not required for protection against EAE, since administration of F(ab')2 fragments fully recapitulated the clinical efficacy of IVIG. F(ab')2-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-γ, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab')2 fragments inhibited adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund's complete adjuvant which is required for induction of active EAE. CONCLUSIONS Our data indicate that F(ab')2-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS.

Osmotischer Druck und Ionenlehre in den medicinischen Wissenschaften. : Zugleich Lehrbuch physikalisch-chemischer Methoden /

Bd. I. Physikalisch-chemische Grundlagen und Methoden. Die Beziehungen zur Physiologie und Pathologie des Blutes.--Bd. II. Circulirendes Blut. Lymphbildung. Hydrops. Resorption. Harn und sonstige Secrete. Elektrochemische Aciditätsbestimmung. Reactions-Verlauf.--Bd. III. Isolirte Zellen. Colloide und Fermente. Muskel- und Nervenphysiologie. Ophtalmologie. Geschmack. Embryologie. Pharmakologie. Balneologie. Bacteriologie. Histologie.

Untersuchungen zur morphologie und physiologie der zelle

hft. 1. Die kerntheilung bei actinosphaerium eichhorni.-hft. 2. Welchen einfluss übt die schwerkraft auf die theilung der zellen?-hft. 3. Das problem der befruchtung und der isotropie des eies, eine theorie der vererbung.-hft. 4. Experimentel- le untersuchungen über die bedingungen der bastardbefruchtung.-hft. 5. Uber den befruchtungs- und teilungsvorgang des tierischen eies unter dem einfluss ausserer agentien.-hft. 6. Experimentelle studien am tierischen ei vor, während und nach der befruchtung. Erster teil.

Die kultur der gegenwart : ihre entwicklung und ihre ziele.

3:4:2 Zellen-und gewebelehre, morphologie unt entwicklungsgeschichte -- v. 3:4:3. Physiologie und ökologie. I. Botanischer teil, unter redaktion von G. Haberlandt. -- v. 3:4:4. Abstammungslehre. Systematik paläontologie. Biogeographie. -- v. 3:5. Anthropologie, unter leitung von G. Schwalbe und E. Fisher. 1923 -- v. 3:7:1. Naturphilosophie, unter redaktion von C. Stumpf. -- v. 4:12. Technik des kriegswesens.

Illinois families now and forever : families by foster care, adoption and guardianship /

Expands the audience served by the Fostering Illinois newsletter (which provided DCFS policy updates and other useful information for foster families), to include adoptive and guardianship families.

Impaired Antigen Presentation and Effectiveness of Combined Active/Passive Immunotherapy for Epithelial Tumors

Background: Although immunization with tumor antigens can eliminate many transplantable tumors in animal models, immune effector mechanisms associated with successful immunotherapy of epithelial cancers remain undefined. Methods: Skin from transgenic mice expressing the cervical cancer-associated tumor antigen human papillornavirus type 16 (HPV16) E6 or E7 proteins from a keratin 14 promoter was grafted onto syngeneic, non-transgenic mice. Skin graft rejection was measured after active immunization with HPV16 E7 and adoptive transfer of antigen-specific T cells. Cytokine secretion of lymphocytes from mice receiving skin grafts and immunotherapy was detected by enzyme-linked immunosorbent assay, and HPV16 E7-specific memory CD8(+) T cells were detected by flow cytometry and ELISPOT. Results: Skin grafts containing HPV16 E6- or E7-expressing keratinocytes were not rejected spontaneously or following immunization with E7 protein and adjuvant. Adoptive transfer of E7-specific T-cell receptor transgenic CD8(+) T cells combined with immunization resulted in induction of antigen-specific interferon gamma-secreting CD8(+) T cells and rejection of HPV16 E7-expressing grafts. Specific memory CD8(+) T cells were generated by immunotherapy. However, a further HPV16 E7 graft was rejected from animals with memory T cells only after a second E7 immunization. Conclusions: Antigen-specific CD8(+) T cells can destroy epithelium expressing HPV16 E7 tumor antigen, but presentation of E7 antigen from skin is insufficient to reactivate memory CD8(+) T cells induced by immunotherapy. Thus, effective cancer immunotherapy in humans may need to invoke sufficient effector as well as memory T cells.