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PubMed1984

Use of adoptive transfer and Winn assay procedures in the further analysis of antiviral acquired immunity in mice protected against Friend leukemia virus-induced disease by passive serum therapy.

Previous studies have demonstrated that spleen cells from DBA/2 mice protected against challenge with a leukemogenic dose of Friend leukemia virus (FLV) by passive administration of xenogeneic antiviral or anti-FLV Mr 71,000 viral envelope glycoprotein antisera can adoptively transfer antiviral resistance to unimmunized irradiated syngeneic recipients. In addition, elimination of T-cells by treatment with anti-Thy 1.2 antibodies plus complement had no effect on the ability of spleen cells from serum-protected mice to adoptively transfer antiviral resistance. We now show that similar depletion of B-cells with rabbit anti-mouse immunoglobulin G plus complement or macrophages by adherence to Sephadex G-10 columns also leaves intact the protective capacity of spleen cells from serum-protected mice. That these results reflect the ability of more than one spleen cell population to transfer antiviral resistance rather than the activity of a non-T, non-B, nonmacrophage cell compartment is supported by the finding that purified splenic T- or B-cells alone from serum-protected DBA/2 mice can adoptively transfer antiviral resistance. Given the previously reported effects of sublethal irradiation on FLV leukemogenesis which could potentially complicate the interpretation of adoptive transfer experiments carried out in this system, analogous studies were performed using a Winn-type assay in which putative effector cells were preincubated with virus before inoculation of the mixture in unirradiated mice. These Winn assay experiments yielded identical results in that serum-protected spleen cells again prevented viral leukemogenesis, and the separate elimination of T-cells, B-cells, or macrophages had no effect on their protective activity. In addition, mixed transfer of serum-protected and normal spleen cells also protected irradiated mice against FLV challenge, providing further evidence that this adoptive protection truly reflects the presence of virus-specific effector cells in the spleens of serum-protected mice and not an inability of these spleen cells to replace radiation-sensitive viral target cells in recipient animals, since these should be supplied by the normal spleen cells in the transferred mixture.

Animals↗
PubMed1994

Adoptive transfer of autoimmune diabetes mellitus to athymic rats: synergy of CD4+ and CD8+ T cells and prevention by RT6+ T cells.

We describe the induction and prevention of autoimmune insulin dependent diabetes mellitus (IDDM), and its pathological substrate, insulitis, in congenitally athymic nude rats following injections of major histocompatibility complex (MHC) compatible lymph node T cells. The cells capable of adoptive transfer of autoimmunity were obtained from diabetes resistant (DR) BB rats that had been rendered hyperglycemic by in vivo depletion of the RT6+ regulatory T cell subset. We first established that our adoptive transfer assay system is cell dose- and time dependent and therefore amenable to quantitative analysis. It was also observed that both CD4+ and CD8+ T cells are required for efficient transfer of autoimmunity. The data indicate that, as in the NOD mouse, a synergistic interaction between CD4+ and CD8+ T cells is important for beta cell destruction. Finally, we demonstrated that the admixture of equal numbers of lymph node T cells, 60% of which were RT6+, from intact, non-diabetic DR rats prevented the adoptive transfer of IDDM mediated by diabetogenic T cells from RT6-depleted DR-BB rats. We conclude that an equilibrium between autoreactive and regulatory cells determines the expression of autoimmunity in the DR-BB rat and in the adoptive transfer of diabetes in quantitative analytical systems.

Animals↗
PubMed2000

Adoptive transfer murine model of granulomatous experimental autoimmune thyroiditis.

Experimental autoimmune thyroiditis (EAT) is a chronic inflammatory autoimmune disease that can be induced in genetically susceptible animals by immunization with mouse thyroglobulin (MTg) in an appropriate adjuvant or by the adoptive transfer of MTg-sensitized donor spleen cells, activated in vitro with MTg, into naive recipients. In the adoptive transfer model used in our laboratory, donor cells activated with MTg alone induce a relatively mild chronic lymphocytic form of EAT (L-EAT), in which the thyroid infiltrate consists primarily of mononuclear cells, and the thyroid inflammation persists for several months. When the same donor cells are activated with MTg together with anti-IL-2R and/or IL-12, a more severe and histologically distinct granulomatous form of EAT is induced in recipient mice. In addition to having distinct histopathologic features, granulomatous EAT (G-EAT) differs from L-EAT in that granulomatous thyroid lesions are not chronic. After reaching maximal severity 21 days after cell transfer, G-EAT thyroid lesions either resolve or the thyroids become atrophic and fibrotic by day 35. In this review, the histopathologic features of G-EAT and L-EAT are described, and our studies with the adoptive transfer G-EAT model which have focused on the mechanisms involved in induction of G-EAT in mice, and the evolution of G-EAT lesions to resolution of inflammation or fibrosis, are reviewed.

Adoptive Transfer↗
PubMed1985

Selective localization of tumor-immune spleen cells at the tumor challenge site after adoptive transfer of line 10 tumor immunity in strain 2 guinea pigs.

In this study, the distribution of immune spleen cells was investigated after adoptive transfer of immunity in inbred strain 2 guinea pigs. Spleen cells obtained from line 10 immune donor animals became specifically restimulated in vitro with 3 M KCl-extracted line 10 soluble proteins, but not with 3 M KCl-extracted line 1 or liver proteins. After 4 days culture in vitro, these specifically restimulated immune spleen cells retained their antitumor activity in vivo after adoptive transfer. The specifically restimulated immune spleen cells were radiolabeled with [3H]thymidine, 1 X 10(8) viable cells were adoptively transferred in tumor-bearing guinea pigs, and their distribution was investigated. As controls for the specific localization of the immune cells at the line 10 tumor, the presence of labeled cells was studied in the contralateral transplanted line 1 hepatoma as well as in cellular inflammatory reactions elicited by injection with incomplete Freund's adjuvant (IFA) and complete Freund's adjuvant (CFA). A significantly higher localization of the labeled immune spleen cells in the line 10 tumor and the first and second draining lymph nodes of the line 10 challenge site were found when compared to the influx of these cells in the line 1 tumor and the nontumor antigen-related inflammatory reactions. Because our immune donor animals were immunized with a mixture of line 10 cells and BCG, these animals are immune to both. Line 10 immune spleen cells were restimulated in vitro with PPD and were radiolabeled. These PPD-restimulated immune spleen cells showed no preferential localization at the line 10 tumor challenge site but, as expected, a tendency for localization at the CFA (H37Ra) injection site. Furthermore, PPD-reactive spleen cells from BCG-immunized guinea pigs showed a significantly higher accumulation at the CFA injection site compared to the IFA injection site and the line 10 and line 1 tumor challenge site. From the results, it is concluded that line 10 tumor-immune and BCG-immune spleen cells are two distinct cell populations, and that the existence of cross-reacting antigens between BCG and the line 10 hepatocarcinoma are of no importance for the rejection of the line 10 tumor by immune spleen cells.

Animals↗
PubMed1999

An antigen-targeted approach to adoptive transfer therapy of cancer.

Previous attempts to treat human malignancies by adoptive transfer of tumor-specific CTLs have been limited by the difficulty of isolating T cells of defined antigen specificity. The recent development of MHC class I/antigenic peptide tetrameric complexes that allow direct identification of antigen-specific T cells has opened new possibilities for the isolation and in vitro expansion of tumor-specific T cells. In the present study, we have derived polyclonal monospecific cell lines from circulating Melan-A-specific CTL precursors of HLA-A*0201+ melanoma patients by combining stimulation with recently identified peptide analogues of the immunodominant epitope from the melanoma-associated antigen Melan-A with staining with fluorescent HLA-A*0201/Melan-A peptide tetramers. In vitro expansion of antigen-specific CD8+ T cells was monitored by flow cytometry with the fluorescent tetramers and anti-CD8 monoclonal antibody. This analysis revealed that Melan-A 26-35 peptide analogues were much more efficient than the parental peptides in stimulating a rapid in vitro expansion of antigen-specific CD8+ T cells. These cells were then isolated by tetramer-guided cell sorting and subsequently expanded in vitro by mitogen stimulation. The resulting polyclonal but monospecific CTLs fully cross-recognized the parental peptides and were able to efficiently lyse Melan-A-expressing tumor cells. Altogether, these results pave the way to a molecularly defined approach to antigen-specific adoptive transfer therapy of cancer.

Antigens, Neoplasm↗
PubMed1976

Quantitative aspects of abolition of transplantation tolerance by the adoptive transfer of lymphoid cells.

It was found that with neonatally induced transplantation tolerance about 50% of the rats are insensitive, or little sensitive, to the adoptive transfer of immunity. The proportion of rejected and unrejected skin grafts in individual experiments did not show a direct dependence on the dose of transferred cells, and immune lymphocytes were as effective as non-immune cells. No dependence on the time post-transplantation was found. Only the results of the adoptive transfers performed after more than 120 days after transplantation indicated an increased resistance of the tolerant state. Also repeated transfers in which increasing doses of cells were used showed a relatively stable state of tolerance in some animals. It is discussed that the difference in the sensitivity to the adoptive transfer might reflect at least quantitative individual differences in the mechanism of the state of unresponsiveness in neonatally induced tolerance.

Animals↗
PubMed1989

Activation requirements of donor T cells and host T cell recruitment in adoptive transfer of murine experimental autoimmune orchitis (EAO).

The relative roles of donor and host T lymphocytes and the T cell activation requirements in adoptive transfer of experimental autoimmune orchitis (EAO) in (C57BL/6 x A/J)F1 mice were investigated in order to gain an understanding of the pathogenesis of this disease. Depletion of T cell subsets in recipients by adult thymectomy and treatment with monoclonal antibodies against CD4 or CD8 had no effect on the incidence of EAO following adoptive transfer of activated T cells from donors immunized with testis homogenate (TH) and adjuvants. In contrast, such depletion of CD4+ T cells inhibited development of EAO in actively immunized mice. Thus, CD4+ cells are required for induction of EAO, but donor CD4+ cells are sufficient by themselves without a comparable contribution from the recipient. Adoptive transfer of EAO required that donor splenic and lymph node T cells be activated in vitro before transfer. We found that exposure to antigen (TH) for as little as 4 hr allowed EAO to occur in 25% of recipients, and by 24 hr the cells were fully competent to induce disease. Proliferation of the cells could not be measured until 2 days later. In serial double-transfer experiments, it was found that the cells must be cultured with TH before each transfer in order for the secondary recipients to develop EAO. However, it was not necessary for the transferred T cells to "see" antigen in vivo in the primary recipients, since transfer to castrated primary recipients had no effect on EAO incidence in secondary recipients. Lymphocytes isolated from diseased testes of immunized donors were competent to transfer EAO without activation in vitro, suggesting that, unlike spleen and lymph node cells, these orchitic lymphocytes were already capable of trafficking to the testis.

Animals↗
PubMed1994

Selective reconstitution of CD8+ cytotoxic T lymphocyte responses in immunodeficient bone marrow transplant recipients by the adoptive transfer of T cell clones.

The adoptive transfer of T cells specific for antigens encoded by pathogens and tumors has been an effective treatment for infections and malignancies in animal models and is potentially applicable for infections occurring in immunodeficient bone marrow transplant recipients. This article reviews recent insights derived from studies of the immunobiology of human cytomegalovirus (CMV) infection in healthy and immunodeficient hosts and the development of adoptive immunotherapy as prophylaxis for CMV infection in recipients of allogeneic bone marrow transplants.

Animals↗
PubMed1995

Nonresponsiveness of AKR.H-2b congenic mice for anti-AKR/Gross MuLV CTL responses: involvement of inhibitory cells as defined by adoptive transfer experiments.

AKR.H-2b mice are unable to elicit AKR/Gross murine leukemia virus (MuLV)-specific cytolytic T lymphocyte (CTL) responses. The participation of inhibitory cells was addressed through adoptive transfer experiments utilizing young AKR.H-2b:Fv-1b congenic responder mice as the recipients of AKR.H-2b donor cells. The adoptive transfer of unfractionated viable splenocytes led to inhibition of virus-specific CTL responsiveness without affecting minor histocompatibility or allogeneic (H-2d)-specific CTL responses. Negative cell selection studies indicated that of the donor AKR.H-2b spleen cells that mediate specific inhibition, B lymphocytes, CD4-CD8+ and CD4+CD8- T lymphocytes, but not macrophages, even though they are viral antigen positive (as are B and T lymphocytes), were the cells responsible for the diminution of the generation of AKR/Gross virus-specific CTL by AKR.H-2b:Fv-1b mice. To evoke maximal inhibition, the adoptive transfer of AKR.H-2b cells had to be performed prior to in vivo priming with viral antigen. Anti-AKR/Gross MuLV nonresponsiveness of AKR.H-2b mice could not be overcome through utilization of exogenous IL-2 at either the priming or in vitro restimulation phases of CTL generation. These results illustrate the complex interaction between retroviruses and lymphocytes and are relevant to understanding how retrovirus-infected cells may not only escape immune surveillance themselves, but also may inhibit the cytolytic T cell response directed at other infected cells, such as tumor cells.

AKR murine leukemia virus↗
PubMed1994

Syngeneic adoptive transfer of anti-human immunodeficiency virus (HIV-1)-primed lymphocytes from a vaccinated HIV-seronegative individual to his HIV-1-infected identical twin.

Immunotherapy by adoptive transfer of lymphocytes was attempted in identical twins, one who was virus-free and the other who was infected with human immunodeficiency virus-1 (HIV-1), at the stage of acquired immunodeficiency syndrome. The noninfected twin was vaccinated by priming with a recombinant vaccinia virus expressing the envelope glycoprotein of one of his brother's viruses and boosting with the same purified gp160 adsorbed on alum. Vaccination elicited major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes specific for HIV-1, but no antibody response. The diseased brother, a 38-year-old homosexual who had developed repeated opportunistic infections since 1990 and had a CD4+ count reduced to practically zero, was treated by infusions of lymphocytes collected from the vaccinated brother by lymphopheresis. After a first transfer of the whole lymphocyte population, no changes were observed in the clinical status and biologic or virologic parameters. A second transfer was then applied with activation of the cells with purified envelope glycoprotein before infusion. The outcome of the treatment was an increase in total lymphocytes, in CD4+ and activated CD8+ DR+ cell counts, and in proliferative responses to HIV antigens. A marked but transient 3-log increase in cellular and plasmatic virus loads was also observed after the second adoptive transfer. These observations will be considered with attention to improve the future adoptive transfer protocols, especially in patients with severe CD4+ depletion.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Unrepresentative behavior of T cell receptor-transgenic CD4+ T cells upon adoptive transfer: lack of need for priming and an extended booster dose-response.

The response of CD4+ T cells taken from DO11.10 alpha beta TCR-transgenic mice to their specific antigen, ovalbumin, was examined in an adoptive transfer system. Read out was the % frequency of KJI-26.1+ (clonotype positive) cells within the Thy-1.2+ (T cell) population in lymph nodes. Control experiments indicated that these cells were uniformly CD4+. Immunizing the transgenic mice had no detectable effect on this frequency. Furthermore, the frequency in recipients of adoptively transferred lymph node cells was not affected by priming of the donors with ovalbumin by various procedures. Transfers were into syngeneic SCID recipients, except in one experiment, where irradiated recipients were shown to behave in the same way. Examining the effect of varying the amount of booster antigen, the response increased slowly with dose, up to a plateau in the range of 10-100 mg ovalbumin. The lack of need for priming is unusual, in comparison with an adoptive transfer of non-transgenic cells, as is the extended dose response range with such a high optimum dose. This enhanced responsiveness is interpreted in terms of a lack of down-immunoregulation in these transgenic mice.

Adoptive Transfer↗
PubMed2006

Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping.

The aim of this study was to determine the effect of adoptive transfer of regulatory natural killer T (NKT) lymphocytes on the metabolic disorder in leptin-deficient ob/ob mice, which feature depletion and defective function of NKT and CD4 lymphocytes. Leptin-deficient ob/ob mice were subjected to transplantation of 1 x 10(6) of either ob/ob or wild-type-derived NKT lymphocytes, or to transplantation of either ob/ob or wild-type-derived splenocytes. The effect on hepatic fat content was measured by magnetic resonance imaging (signal intensity index) and histology, using the steatohepatitis grading scale. The degree of glucose intolerance was measured by an oral glucose tolerance test (GTT). Adoptive transfer of wild-type or ob/ob-derived regulatory NKT cells led to a 12% decrease in hepatic fat content. A significant histological shift from macrosteatosis to microsteatosis was observed. Marked improvement in the GTT was noted in wild-type or ob/ob-derived NKT recipients. Metabolic effects were associated with a significant decrease in peripheral and intrahepatic CD4/CD8 lymphocyte ratios. Intrahepatic CD8 trapping was observed in all responders. Serum interleukin 10 levels decreased significantly. In conclusion, adoptive transfer of a relatively small number of regulatory NKT lymphocytes into ob/ob mice results in a significant reduction in hepatic fat content, a shift from macro to microsteatosis, and significant improvement in glucose intolerance. These effects were associated with decreased peripheral and intrahepatic CD4/CD8 ratios and decreased interleukin 10 levels. The results further support a role for regulatory NKT lymphocytes in the pathogenesis of non-alcoholic steatohepatitis in the leptin-deficient murine model.

Adoptive Transfer↗
PubMed2006

Adoptive transfer of paternal antigen-hyporesponsive T cells facilitates a Th2 bias in peripheral lymphocytes and at materno-fetal interface in murine abortion-prone matings.

PROBLEM: To investigate the Th1/Th2 cytokine changes in abortion-prone recipient mice adoptively transferred by the paternal antigen-hyporesponsive T cells. METHOD OF STUDY: The paternal antigen-hyporesponsive T cells were generated by the anti-B7 monoclonal antibody (mAb) treatment and adoptively transferred into pregnant CBA/J mice of abortion-prone matings on day 4 of gestation. The intracellular expressions of Th1 cell-derived cytokine, tumor necrosis factor-alpha, gamma-interferon and interleukin-2 (IL-2) and Th2 cell-derived cytokine, IL-4 and IL-10 in the maternal spleen were analyzed by flow cytometry, and secretions of the Th1 and Th2 cytokines in supernatant of the feto-placental unit culture were analyzed by an enzyme-linked immunosorbent assay. RESULTS: Our findings showed the increased secretion of Th1 cytokines and the decreased secretion of Th2 cytokines in abortion-prone matings. Treatment with anti-B7 mAbs on day 4 of gestation enhanced Th2 and reduced Th1 cytokine production in abortion-prone matings. Similarly, adoptive transfer of paternal antigen-hyporesponsive T cells induced maternal tolerance to the fetus and displayed a Th2 bias both in the peripheral lymphocytes and at the materno-fetal interface of the abortion-prone matings. CONCLUSIONS: These findings indicate that the Th2 cytokine bias and an increase in fetal viability induced by the anti-B7 mAb treatment can be transferred to other pregnant mice of the abortion-prone matings.

Abortion, Spontaneous↗
PubMed2000

Induction of experimental autoimmune keratitis by adoptive transfer of human corneal antigen-specific T-cell line.

PURPOSE: To establish a permanent human corneal antigen (HuCOAg)-specific T-cell line and to determine whether line cells are capable of inducing inflammatory keratitis by adoptive transfer. METHODS: Lymphoid cells harvested from HuCOAg-immunized Lewis rats were expanded to a permanent T-cell line by repetitive cycles of restimulation with HuCOAg and irradiated antigen-presenting cells and propagation in interleukin 2-containing medium. The phenotype and epitope specificity of the line cells were determined. Adoptive transfer was performed after seven cycles by intraperitoneal injection of activated T cells into irradiated recipient rats. RESULTS: A panel of 11 overlapping synthetic HuCOAg peptides to identify T-cell epitopes recognized by the line cells was used. The cells responded selectively to a synthetic peptide containing an immunodominant epitope of HuCOAg (peptides 69-83). Line cells bore the surface phenotype of the T-helper/inducer marker (W 3/25(+) or CD4(+)). Intraperitoneal inoculation of naive rats with 5 x 10(7) activated line cells led to maximal clinical signs of stromal keratitis 7 to 9 days after transfer, characterized by corneal haze, conjunctival and episcleral injection, corneal infiltrates, and neovascularization. Histopathologic examination of the tissues revealed numerous lymphocytes and macrophages and some polymorphonuclear leukocytes along with neovascularization. The pathologic lesions were confined to the peripheral corneal stroma. Immunohistochemical studies demonstrated that the overwhelming majority of the inflammatory cells were CD4(+) T lymphocytes and macrophages; an upregulation of major histocompatibility complex class II antigen expression was also noted. CONCLUSIONS: A long-term, rat T-cell line of CD4(+) phenotype specific for HuCOAg that can induce autoimmune keratitis by adoptive transfer of the line cells to naive syngeneic recipients is described. With the development of this cell line, the mechanisms by which T cells exert their immunopathologic effects in experimental autoimmune keratitis models can be studied.

Adoptive Transfer↗
PubMed1981

Immunity to Strongyloides ratti in rats. 1. Adoptive transfer with mesenteric lymph node cells.

Adoptive transfer of immunity against the enteral phase of Strongyloides ratti was monitored using four parameters; namely, number of worms recovered, position occupied in the host's small intestine, worm length and fecundity. When immune mesenteric lymph node cells (IMLNC) were transferred from donors infected for 20, 26 or 32 days into recipients infected for 3 days, a marked acceleration of worm expulsion was evident by day 16 post-infection (p.i.). IMLNC from day-16 p.i. donors did not transfer expulsion. In an experiment in which recipients were given 2 x 10(8) or 1 x 10(8) IMLNC from donors infected for 26 days, accelerated worm expulsion occurred only with the higher inoculum, although manifestations of direct worm immunity, i.e. altered position and reduced length and fecundity, were evident in both cases. Transfer of IMLNC appeared to have no effect upon worm establishment; when cells were transferred on the day of infection a period of 16 days was necessary to effect both direct anti-worm immunity and expulsion, although the former was evident on day 14 p.i. However, when IMLNC were transferred to rats already infected for 6 days, a very significant reduction of their worm burden was apparent 10 days after IMLNC transfer.

Animals↗
PubMed1985

Eradication of a disseminated syngeneic mouse lymphoma by systemic adoptive transfer of immune lymphocytes and its dependence upon a host component(s).

We have studied the in vivo effects of carrageenan and trypan blue on the adoptive immunotherapy of an established local and disseminated syngeneic mouse FBL-3 lymphoma. Mice receiving 500 rads total-body irradiation before injection of FBL-3 tumor into the footpad were treated 4 to 5 days later when a palpable local tumor and disseminated metastases were present. Injection of in vivo immune lymphocytes i.v. caused complete regression of footpad tumor and cured 96% of all mice (greater than 60 days mean survival; p less than 0.0005). Carrageenan or trypan blue treatment of the tumor-bearing host abrogated the therapeutic effect of adoptively transferred cells. Cure rates were significantly reduced to 27% (p less than 0.004) and 0% (p less than 0.0001) and mean survival times to 40.2 days (p less than 0.0005) and 15.2 (p less than 0.005) days for mice treated with carrageenan and trypan blue, respectively, in addition to immune cells. In vivo treatment of the immune spleen cell donors with carrageenan or trypan blue had no significant effect on the ability of those splenocytes to mediate cure when adoptively transferred into tumor-bearing hosts, indicating that the inhibitory activity of these agents cannot be attributed to direct toxicity to immune lymphoid cells. These results demonstrate that a recipient component(s), possibly macrophages, sensitive to carrageenan and to trypan blue but relatively resistant to radiation (500 rads), plays a vital role in the cure of tumor-bearing mice that receive the adoptive transfer of immune splenocytes.

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↗
PubMed2003

Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants.

Adoptive transfer of cytomegalovirus (CMV)-specific T cells can restore long-lasting, virus-specific immunity and clear CMV viremia in recipients of allogeneic stem cell transplants if CD4(+) and CD8(+) CMV-specific T cells are detected in the recipient after transfer. Current protocols for generating virus-specific T cells use live virus, require leukapheresis of the donor, and are time consuming. To circumvent these limitations, a clinical-scale protocol was developed to generate CMV-specific T cells by using autologous cellular and serum components derived from a single 500-mL blood draw. CMV-specific T cells were stimulated simultaneously with CMV-specific major histocompatibility complex class I (MHC I)- restricted peptides and CMV antigen. Activated T cells were isolated with the interferon-gamma (IFN-gamma) secretion assay and expanded for 10 days. In 8 randomly selected, CMV-seropositive donors, 1.34 x 10(8) combined CD4(+) and CD8(+) CMV-specific T cells, on average, were generated, as determined by antigen-triggered IFN-gamma production. CMV-infected fibroblasts were efficiently lysed by the generated T cells, and CMV-specific CD4(+) and CD8(+) T cells expanded if they were stimulated with natural processed antigen. On the other hand, CD4(+) and CD8(+) T cell-mediated alloreactivity of generated CMV-specific T-cell lines was reduced compared with that of the starting population. In conclusion, the culture system developed allowed the rapid generation of allodepleted, highly enriched, combined CD4(+) and CD8(+) CMV-specific T cells under conditions mimicking good manufacturing practice.

Adoptive Transfer↗