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PubMed2004

Potentiation of tumor eradication by adoptive immunotherapy with T-cell receptor gene-transduced T-helper type 1 cells.

Adoptive immunotherapy using antigen-specific T-helper type 1 (Th1) cells has been considered as a potential strategy for tumor immunotherapy. However, its application to tumor immunotherapy has been hampered by difficulties in expanding tumor-specific Th1 cells from tumor-bearing hosts. Here, we have developed an efficient protocol for preparing mouse antigen-specific Th1 cells from nonspecifically activated Th cells after retroviral transfer of T-cell receptor (TCR)-alpha and TCR-beta genes. We demonstrate that Th1 cells transduced with the TCR-alpha and -beta genes from the I-A(d)-restricted ovalbumin (OVA)(323-339)-specific T-cell clone DO11.10 produce IFN-gamma but not interleukin-4 in response to stimulation with OVA(323-339) peptides or A20 B lymphoma (A20-OVA) cells expressing OVA as a model tumor antigen. TCR-transduced Th1 cells also exhibited cytotoxicity against tumor cells in an antigen-specific manner. Moreover, adoptive transfer of TCR-transduced Th1 cells, but not mock-transduced Th1 cells, exhibited potent antitumor activity in vivo and, when combined with cyclophosphamide treatment, completely eradicated established tumor masses. Thus, TCR-transduced Th1 cells are a promising alternative for the development of effective adoptive immunotherapies.

Animals↗
PubMed2006

Mechanism of inflammation in murine eosinophilic myocarditis produced by adoptive transfer with ovalbumin challenge.

BACKGROUND: Interleukin (IL)-5, RANTES and CC chemokine receptor 3 (CCR3) are essential for induction of eosinophil recruitment in organs, but the precise pathogenesis of eosinophilic myocarditis is still unclear. We investigated the relationships between these cytokines and receptors in the development of inflammation in murine myocarditis produced by adoptive transfer, with reference to eosinophil infiltration and signal transduction. METHODS: The splenocytes from male donor DBA/2 mice were separated after ovalbumin (OVA) sensitization. These cells had a CD4/CD8 ratio of approximately 3.0. Cells (2.0 x 10(7)) were individually transfused to recipient adoptive male DBA/2 mice, and OVA challenge was performed serially. The heart and spleen of the recipient were analyzed to determine the kinetics of IL-5, RANTES, CCR3 and eosinophil production with simultaneous determination of Janus kinase 3 (JAK3) mRNA. RESULTS: Approximately 85% of recipient mice developed myocarditis; 35% had recognizable cell infiltration in the left ventricular endocardium, an effect which was absent in control mice. Eosinophilic myocarditis was usually associated with animals having several degenerative changes in myocardial cells, and IL-5, RANTES and CCR3 expressions were usually present in these eosinophils (p < 0.05). CCR3 and JAK3 mRNAs were detected in the spleens and hearts of recipient animals providing histological evidence for kinetics related to eosinophil infiltration. CONCLUSION: The murine model of adoptive transferred myocarditis is suitable for studying the mechanism of eosinophilic myocarditis. A unique pathogenesis of this disorder may be controlled by the synergism of CD4 dominancy in the donor and JAK-STAT signaling in the recipient, which may cause recruitment of eosinophils into heart lesions.

Adoptive Transfer↗
PubMed1992

Adoption of an additional infant by a Western lowland gorilla (Gorilla gorilla gorilla).

A 10-year-old Western lowland gorilla, already caring for her own 14-month-old son, adopted a female neonate. The infant's mother (aged 7 years, 4 months) showed no interest in the infant, and it is unclear whether she abandoned the infant or whether it was seized by the dominant foster-mother. The foster-mother gave more maternal attention to the adoptee than to her own son but gave both infants the same protection. She adjusted her forms of transport to the age of each infant. The subadult mother of the neonate did not seek contact with her offspring during the first 4 weeks and in fact showed more interest in the 14-month-old male infant. Interactions between the two mothers were rare. The foster-mother's own male infant died 2 months after she had adopted the female infant. She looked after the adopted infant for 1 year, but then lost interest so that the adoptee had to be separated.

Adoption↗
PubMed1995

Adoptive transfer of allergic airway responses with sensitized lymphocytes in BN rats.

To evaluate the role of lymphocytes in the pathogenesis of allergic bronchoconstriction, we investigated whether allergic airway responses are adoptively transferred by antigen-primed lymphocytes in Brown Norway (BN) rats. Animals were actively sensitized to ovalbumin (OA) or sham sensitized, and 14 d later mononuclear cells (MNCs) were isolated from intrathoracic lymph nodes, passed through a nylon wool column, and transferred to naive syngeneic rats. Recipients were challenged with aerosolized OA or bovine serum albumin (BSA) (5% wt/vol) and analyzed for changes in lung resistance (RL), airway responsiveness to inhaled methacholine (MCh), and bronchoalveolar lavage (BAL) cells. Recipients of MNCs from sensitized rats responded to OA inhalation and exhibited sustained increases in RL throughout the 8-h observation period, but without usual early airway responses. Recipients of sham-sensitized MNCs or BSA-challenged recipients failed to respond to antigen challenge. At 32 h after OA exposure, airway responsiveness to MCh was increased in four of seven rats that had received sensitized MNCs (p = 0.035). BAL eosinophils increased at 32 h in the recipients of both sensitized and sham-sensitized MNCs. However, eosinophil numbers in BAL were inversely correlated with airway responsiveness in the recipients of sensitized MNCs (r = -0.788, p = 0.036). OA-specific immunoglobulin E (IgE) was undetectable by enzyme-linked immunosorbent assay (ELISA) or passive cutaneous anaphylaxis (PCA) in recipient rats following adoptive transfer. In conclusion, allergic late airway responses (LAR) and cholinergic airway hyperresponsiveness, but not antigen-specific IgE and early responses, were adoptively transferred by antigen-primed lymphocytes in BN rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

CD3+ and CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis.

To characterize the cells responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (EHP), we depleted Micropolyspora faeni (M. faeni)-sensitized C3H/HeJ spleen cell (SC) cultures of CD3+, CD4+, or CD8+ cells before administration to recipients. We determined the length of time sensitization persists, the ability of cultured lung-associated lymph node (LALN) cells to transfer EHP, and the ability of cultured SC from animals subjected to two, four, or eight weekly intratracheal challenges of M. faeni to transfer EHP. The extent of pulmonary inflammatory response after challenge with intratracheal M. faeni was used to determine adoptive transfer. Depletion reduced the proportion of CD3+ cells from 21 to 1%, CD4+ cells from 15 to 3%, and CD8+ cells from 7 to 1% in the cultured SC population. The proportion of B cells exhibited reciprocal changes. Cultured SC could transfer EHP. Depletion of CD3+ and CD4+, but not CD8+ cells, ablated or diminished the capacity to transfer EHP. Sensitized cells persisted in recipients for at least 8 wk. Cultured LALN cells could transfer EHP. Recipients of cultured SC from 4- and 8-wk donors exhibited less extensive pulmonary abnormalities than recipients of cultured SC from 2-wk donors. The proportion of CD3+, CD4+, CD8+, B cells, and macrophages was the same in cultured cells from 2-, 4-, and 8-wk donors. We conclude that the active cells in SC cultures are CD3+, CD4+, and CD8- T cells, and there are differences in the ability of cultured cells to adoptively transfer EHP that are dependent on the nature of the donor but not on the phenotype of the cell population.

Alveolitis, Extrinsic Allergic↗
PubMed1975

The treatment of adopted versus neglected delinquent children in the court: a problem of reciprocal attachment?

The authors investigated the discrepant treatment by a juvenile court of adopted versus neglected delinquents. Adopted delinquents received harsher dispositions in spite of the fact that neglected delinquents often faced more serious charges. The two groups are compared in terms of family structure and the criminal and psychiartic histories of their parents; none of these seems to account for the adoptees' harsher treatment. The authors hypothesize that an interplay of late adoption intrinsic vulnerabilities in the children, and weakness of parental bonds accounts for the differential outcomes.

Adolescent↗
PubMed1987

Genetic contributions to human fatness: an adoption study.

A strong relationship was found between the degree of fatness of biologic mothers and that of their adult offspring who had been separated from their mothers at birth and adopted during the first year of life. This relationship persisted even after age, height, and possible confounding environmental factors were controlled. There was little evidence for either selective placement on the basis of parental fatness or gene-environment interaction. There was no relationship between the degree of fatness of adoptive parents and that of the adoptees. Two indexes of environmental influence--rural upbringing and disturbance in the adoptive home--predicted fatness among adoptees.

Adipose Tissue↗
PubMed2003

Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia.

OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses.

Adoption↗
PubMed1979

Outcome of adopted Vietnamese children. Beneficial effects of a normal home environment on 36 children.

Thirty-six adopted Vietnamese children were evaluated physically and developmentally from four months to ten years after their adoption. All of the children had experienced early months of malnutrition, disease and deprivation. Many of the children were adopted before their first birthdays and received continuous, adequate care from invested families. Only two children had intelligence quotients less than 85 on the Slosson Test. Though physical abnormalities such as residuals of poliomyelitis, ear infections, and soft neurologic signs existed, no child was incapacitated by these conditions. From the data available in the study, developmental outcomes could not be adequately predicted on the basis of unknown genetics, early malnutrition, or early deprivation.

Adoption↗
PubMed1981

Adoption planning for handicapped children. A medical-social work partnership.

Major changes are taking place in the field of adoption. Once concerned primarily with the placement of newborn infants, the field has broadened, with a major emphasis on the adoption of older children, often from foster care and many times with major handicaps or problems. These children require special families who are willing to adopt them. They require the services of skilled social workers to effectively place them, and they require understanding of the physician who may be involved either with their placement examination or with their subsequent management as an adoptee. A new objective approach to the problem is necessary.

Adoption↗
PubMed2007

CpG oligodeoxynucleotides allow for effective adoptive T-cell therapy in chronic retroviral infection.

Adoptive T-cell therapy in cancer or chronic viral infections is often impeded by the development of functional impairment of the transferred cells. To overcome this therapeutic limitation we combined adoptive transfer of naive, virus-specific CD8+ T cells with immunostimulative CpG oligodeoxynucleotides (ODNs) in mice chronically infected with the Friend retrovirus. The CpG-ODN co-injection prevented the T cells from developing functional defects in IFNgamma and granzyme production and degranulation of cytotoxic molecules. Thus, the transferred T cells were able to reduce chronic viral loads when combined with CpG-ODNs. This strategy provides a new approach for developing successful adoptive T-cell therapy against chronic infections.

Animals↗
PubMed2005

Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice.

T-helper cell type 1 (Th1) cells have been postulated to have a significant role in protective immunity against allergic diseases. However, recent studies using polarised Th1 cells showed conflicting effects on both airway responsiveness and eosinophilic inflammation in a mouse asthma model. The current study explored the effects of adoptive transfer of established Th1 clones on a murine model of atopic asthma. Mice (BALB/c) were sensitised with ovalbumin (OVA) and challenged with aerosolised OVA (5%, 20 min) for 5 days. Just before starting the first challenge, Th1 clones (5x10(6) x body(-1)) or PBS alone were injected via the tail vein. After assessment of airway responsiveness to methacholine, bronchoalveolar lavage fluid (BALF) was obtained. Histological examination, including morphometric analysis, measurement of cytokines in the BALF and Northern blotting of lung chemokines, was also performed. Adoptive transfer of Th1 clones showed a significantly increased total number of cells, whereas significantly decreased eosinophils were found in the BALF, when compared with mice with injection of vehicle alone or splenic mononuclear cells. Administration of Th1 clones significantly decreased the infiltration of eosinophils but increased mononuclear cells in the peribronchial area. Goblet cell hyperplasia and peribronchial fibrosis were also suppressed by Th1 clones. The transfer of Th1 cells significantly decreased airway responsiveness. Th1 injection significantly increased interferon gamma in the BALF, but significantly decreased interleukin (IL)-5 and IL-13. Eotaxin mRNA was predominantly expressed in the lungs of asthma model mice, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) predominates in such mice with Th1 transfer. In conclusion, results suggest that the adoptive transfer of T-helper cell type 1 clones can suppress both lung eosinophilia and airway responsiveness, but increase noneosinophilic inflammation in a mouse model of asthma.

Adoptive Transfer↗
PubMed2006

Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma.

PURPOSE: The adoptive transfer of in vitro generated tumor antigen-specific cytotoxic T lymphocytes (CTL) provides a promising approach to the immunotherapy of cancer. A phase I study was conducted to test the feasibility, safety, and survival of adoptively transferred Melan-A-specific CTL lines in melanoma patients. PATIENTS AND METHODS: Eleven HLA-A2+ patients with metastatic melanoma received at least three intravenous infusions of Melan-A-specific CTL at 2-week intervals. CTL were generated by four rounds of in vitro stimulation of purified CD8+ peripheral blood lymphocytes with autologous dendritic cells pulsed with an HLA-A2 binding Melan-A peptide. Each T-cell infusion was accompanied by a 6-day course of low-dose interleukin-2. RESULTS: A total of 52 T-cell infusions were administered, averaging 2.1 x 10(8) Melan-A-specific CTL per infusion. Clinical adverse effects were mild and consisted of chills and low-grade fever in seven of 11 patients. Clinical and immunologic responses revealed an antitumor response in three of 11 patients (one complete regression, one partial regression, one mixed response), an elevated frequency of circulating Melan-A tetramer+ T cells up to 2 weeks in all the patients with a maximal frequency of 2% of total CD8+ T cells, an increase in eosinophils to up to 50% in seven of 11 patients, and a selective loss of Melan-A expression in lymph node metastases in two evaluated patients after T-cell transfer. CONCLUSION: Our data indicate that the adoptive transfer of antigen-specific T cells in melanoma patients can induce clinical tumor-specific immune responses without major adverse effects.

Adult↗
PubMed1997

Trafficking of adoptively transferred B lymphocytes in B-lymphocyte-deficient mice.

Many studies have investigated the fate of adoptively transferred lymphocytes in recipient mice, although little is known of the sites where these transferred cells reside at particular time points. Using flow cytometry, we analyzed the trafficking pattern of adoptively transferred naive B cells into the lymphoid organs of syngeneic B-cell-deficient (microMT) mice. Within the first 24 h of transfer, the location of B cells was highly dependent on the mode of B-cell transfer. When B cells were injected subcutaneously into microMT mice, they showed a different trafficking pattern from cells administered into the peritoneal cavity or injected intravenously. After subcutaneous transfer into the thigh, the greatest number of B cells was detected in the popliteal lymph node nearest to the injection site, whereas the lowest number was detected in the axillary lymph node opposite to the injection side. Within the first 24 h of either intraperitoneal and intravenous injection, B cells were found in approximately equal numbers in the lymph nodes and the spleen. Two days later, the B-cell distribution in the lymphoid organs appeared to be independent of the mode of B-cell transfer. A transient decrease in the numbers of splenic and lymph node B cells occurred 9 days after B-cell transfer (a decrease from 70 to 87%) prior to the outgrowth of B cells that occurs 21 days after transfer. These studies are useful for understanding the numbers of B cells that may be required in adoptive transfer studies and their potential cellular interactions at particular physiological sites based on the route of cell transfer.

Adoptive Transfer↗
PubMed1999

The Oedipus complex revisited: Oedipus abandoned, Oedipus adopted.

The author considers that the Oedipus of Sophocles' drama, who kills his biological father and marries his biological mother, is an illustration of the failure to work through the complex named after him. She draws attention to the contrast between the obscurity that surrounds the hero's adoptive parents and the notoriety of their biological counterparts arguing that the former are equally important in the universal oedipal fantasy. In her view the fact that Oedipus has two sets of parents--abandoning and adopting respectively--is significant in that the resulting dichotomisation of the parental imago enables him seemingly to avoid a conflict of ambivalence in relation to a single object. The author further contends that the plague of Thebes represents the symptomatic return of repressed or disavowed aggression. Three clinical examples reveal the parental imago's division to be an unconscious defence against oedipal anxieties and the sense of solitude vis-à-vis the intimacy of the parental couple. The working through of the Oedipus complex is stated to require the synthesis of love and hate and of the abandoning and adoptive aspects of the parents whereby the formerly sadistic superego becomes protective. The author also argues that a useful distinction can be made between splitting and dichotomisation.

Adoption↗
PubMed2006

"He won't be my son": Middle Eastern Muslim men's discourses of adoption and gamete donation.

In the Sunni Muslim world, religious mandates prohibit both adoption and gamete donation as solutions to infertility, including in the aftermath of in vitro fertilization (IVF) failures. However, both of these options are now available in two Middle Eastern countries with significant Shi'ite Muslim populations (Iran and Lebanon). On the basis of fieldwork in multisectarian Lebanon, I examine in this article attitudes toward both adoption and gamete donation among childless Muslim men who are undertaking IVF with their wives. No matter the religious sect, most Muslim men in Lebanon continue to resist both adoption and gamete donation, arguing that such a child "won't be my son". However, against all odds, some Muslim men are considering and undertaking these alternatives to family formation as ways to preserve their loving marriages, satisfy their fatherhood desires, and challenge religious dictates, which they view as out of step with new developments in science and technology. Thus, in this article I examine the complicated intersections of religion, technology, marriage, and parenthood in a part of the world that is both poorly understood and negatively stereotyped, particularly in the aftermath of September 11, 2001.

Adoption↗
PubMed2006

Economic analysis of prevaccination serotesting compared with presumptive immunization for polio, diphtheria, and tetanus in internationally adopted and immigrant infants.

BACKGROUND: No consensus exists about whether to conduct prevaccination serotesting or to presumptively vaccinate internationally adopted and immigrant infants with inactivated polio (IPV) and diphtheria-tetanus-acellular pertussis (DTaP) immunizations. OBJECTIVE: To study the clinical and economic outcomes from a societal perspective of prevaccination serotesting in a hypothetical 12-month-old internationally adopted or immigrant infant. DESIGN AND METHODS: A decision analysis model was developed comparing presumptive vaccination with IPV versus serotesting for poliovirus type 1, 2, and 3 antibodies followed by vaccination in unprotected patients. A similar decision analysis model was developed comparing presumptive vaccination with DTaP versus serotesting for diphtheria and tetanus toxoid antibodies. The main outcome measures were cost per patient protected from polio, diphtheria, and tetanus. RESULTS: Compared with presumptive immunization, prevaccination serotesting for polio increases the cost per patient from $57 to $62 and decreases the percentage of patients protected against polio from 95.3% to 94.0%. Serotesting for diphtheria and tetanus increases the cost per patient from $62 to $119 and increases the percentage of patients protected against both diphtheria and tetanus from 91.5% to 92.3%. Presumptive immunization with DTaP costs less and is more clinically effective than serotesting if >80% of patients do not complete the full vaccine series or if antibody seroprevalence to both diphtheria and tetanus is <51%. CONCLUSIONS: Presumptive immunization for polio improves outcomes and saves costs compared with prevaccination serotesting in internationally adopted and immigrant infants. The results for DTaP are less definitive, although immunization is the preferred strategy in populations with poor vaccine compliance or low seroprevalence of antibodies to diphtheria and tetanus.

Adoption↗
PubMed1995

Adoptive immunotherapy for primary lung cancer.

The data presented in the present clinical trial demonstrated that adoptive immunotherapy using IVS cells and alpha CD3-AT cells for primary lung cancer patients may have therapeutic efficacy in selected groups of patients. Further investigation, such as induction of cytokine genes into effector cells to maximize the in vivo anti-tumor activity, combination of active immunization (tumor vaccine) and adoptive immunotherapy (10) would be definitely required for utilization of adoptive immunotherapy for lung cancer.

Adult↗