Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Adoptive Transfer”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2000

The fate of adoptively transferred quiescent encephalitogenic T cells in normal and antigen-tolerized mice.

Adoptive transfer of quiescent encephalitogenic T cells to normal syngeneic recipients was without clinical effect. RT-PCR was used to assess localization of an adoptively transferred quiescent encephalitogenic T cell clone in normal and antigen-unresponsive mice prior to or after challenge with neuroantigen/CFA. The T cell clone was not detectable in lymphoid tissues prior to challenge with neuroantigen; however, following challenge, the clone was found in the spleen, lymph nodes and spinal cord of both normal and antigen-tolerized mice. The latter animals remained clinically normal. Non-activated encephalitogenic T cells transferred to wild-type recipients pretreated i.p. with neuroantigen/IFA were rendered unresponsive. Transfer of the same T cells to alpha/beta T cell-deficient mice pretreated with neuroantigen/IFA resulted in spontaneous disease indicating that an intact alpha/beta T cell system was required for development of the unresponsive state.

Adoptive Transfer↗
PubMed2003

Adoptive transfer of ex vivo immune-programmed NKT lymphocytes alleviates immune-mediated colitis.

T lymphocyte-expressing natural killer (NK) cell markers (NKT cells) play a role in immune regulation. Our aim was to evaluate the in vivo effect of adoptive transfer of immune-programmed NKT cells. Colitis was induced in C57/B6 mice by 2,4,6-trinitrobenzenesulfonic acid. NKT, CD4, CD8 lymphocytes, and dendritic cells (DC) were prepared from spleens of naive mice, animals with colitis, and animals with colitis that were orally tolerized. Subsets of splenocytes, NKT, CD4, and CD8 and NKT+CD4, NKT+CD8, and NKT+DC lymphocytes were prepared. Assessment of the T helper cell type 1 (Th1)/Th2 cytokine secretion paradigm in vitro was performed before and following exposure to the antigen. Adoptive transfer of ex vivo immune-programmed lymphocytes from each group was performed into recipient mice, followed by colitis induction. Ex vivo exposure of NKT cells harvested from mice with colitis-to-colitis proteins [colitis-extracted proteins (CEP)] led to a Th2 cytokine shift. The interleukin (IL)-4/interferon-gamma (IFN-gamma) ratio increased for NKT harvested from colitis-harboring mice following exposure to CEP. Adoptive transfer of NKT lymphocytes harvested from colitis-harboring mice, which were ex vivo-educated, significantly alleviated experimental colitis in vivo. Intrahepatic NKT lymphocytes increased significantly in mice transplanted with NKT lymphocytes harvested from colitis-harboring donor mice, which were ex vivo-exposed to CEP, similar to mice transplanted with NKT lymphocytes harvested from tolerized donors. Exposure of NKT cells to the disease-target antigen induced a significant increase in the IL-4/IFN-gamma cytokine ratio. Adoptive transfer of a relatively small number of immune-programmed NKT cells induced a systemic Th1 to Th2-immune shift and alleviated immune-mediated colitis.

Adoptive Transfer↗
PubMed1992

Use of recombinant interleukin-2 to enhance adoptive transfer of resistance to Listeria monocytogenes infection.

In vitro incubation of Listeria-immune spleen cells (LISC) with recombinant interleukin-2 (rIL-2) for at least 3 days increased their ability to transfer antilisteria resistance to recipient mice. This effect was blocked by the in vitro addition of transforming growth factor beta 1. The level of protection afforded by the transfer of rIL-2-incubated LISC was further elevated by the in vivo administration of rIL-2 at a dose that by itself did not significantly increase antilisteria resistance. The antilisteria resistance of recipient mice remained elevated for approximately 7 days and then rapidly declined to undetectable levels by 10 days. After cell transfer, recipient mice were protected against challenge with Listeria monocytogenes but not Salmonella typhimurium, Yersinia enterocolitica, or Streptococcus pyogenes. Flow cytometric analyses revealed an increase in the percentages of CD8+, NK+, and gamma delta T cell receptor+ cells but no change in the percentage of CD4+ cells as a result of LISC coculturing with rIL-2. In vitro depletion of CD4+ cells just prior to transfer had no significant effect on the adoptive transfer of resistance; depletion of CD8+ cells reduced the level of resistance by approximately 25%. Combined depletion of Thy-1.2+, CD4+, and CD8+ cells just prior to adoptive transfer diminished the level of protection in the spleens but not the livers of recipient mice. These data suggest that rIL-2 can be used to augment adoptive immunotherapy for bacterial infection in a manner similar to adoptive immunotherapy of human cancer patients. Although the protective cell population was not definitively identified, it appeared to be independent of CD4+ cells and only partly dependent on CD8+ cells.

Animals↗
PubMed2006

A simple method for unbiased quantitation of adoptively transferred cells in solid tissues.

In a mouse model, we demonstrate how to obtain a direct, unbiased estimate of the total number of adoptively transferred cells in a variety of organs at different time points. The estimate is obtained by a straightforward method based on the optical fractionator principle. Specifically, non-stimulated C57BL/6J mouse splenocytes were labelled with carboxyfluorescein diacetate succinimidyl ester (CFSE) and adoptively transferred to normal C57BL/6J mice by intravenous injection. The total number of CFSE-positive cells was subsequently determined in lung, spleen, liver, kidney, and inguinal lymph node at six different time points following adoptive transfer (from 60 s to 1 week), providing a quantitative estimate of the organ distribution of the transferred cells over time. These estimates were obtained by microscopy of uniform samples of thick sections from the respective organs. Importantly, the samples were chosen and prepared in accordance with the optical fractionator principle. We demonstrate that the method is simple, precise, and well suited for quantitative immunological studies.

Adoptive Transfer↗
PubMed2003

Adoptive transfer studies demonstrate that macrophages can induce proteinuria and mesangial cell proliferation.

BACKGROUND: Glomerular macrophage accumulation is a feature of proliferative human and experimental glomerulonephritis. However, our understanding of the role of macrophages in the induction of renal injury is based upon indirect evidence from depletion studies, most of which lack specificity for this cell type. Therefore, an adoptive transfer approach was used to directly assess the potential of macrophages to induce renal injury. METHODS: Accelerated anti-glomerular basement membrane (anti-GBM) disease was induced in rats by immunization with sheep IgG (day -5), followed by administration of sheep anti-rat GBM serum (day 0), with animals killed on day 2. To facilitate the adoptive transfer studies, immunized animals were made leukopenic by cyclophosphamide (CyPh) given on day -2. Bone marrow-derived (BM) or NR8383 macrophages were transferred by tail vein injection 24 hours after injection of anti-GBM serum, with animals killed 3 or 24 hours after transfer. RESULTS: Pretreatment with CyPh prevented glomerular leukocyte accumulation and completely inhibited proteinuria, glomerular cell proliferation and hypercellularity in accelerated anti-GBM disease. Adoptive transfer led to significant glomerular accumulation of BM or NR8383 macrophages within 3 hours of injection, and this was still evident 24 hours later. Adoptive transfer of BM or NR8383 macrophages induced proteinuria (63 +/- 16 BM vs. 5 +/- 2 mg/24 h CyPh control; P < 0.001), glomerular cell proliferation (5.1 +/- 1.2 BM vs. 0.5 +/- 0.1 PCNA+ cells/gcs CyPh; P < 0.001) and glomerular hypercellularity (51.2 +/- 2.0 BM vs. 41.9 +/- 0.9 nuclei/gcs CyPh; P < 0.001). The degree of renal injury correlated with the number of transferred glomerular macrophages. Two-color immunostaining demonstrated that most glomerular proliferative cell nuclear antigen+ (PCNA+) proliferating cells were OX-7+ mesangial cells. CyPh treatment did not prevent up-regulation of glomerular intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) expression or an increase in urinary monocyte chemoattractant protein-1 (MCP-1) excretion. CONCLUSION: This study provides the first direct evidence that macrophages can induce renal injury in terms of proteinuria and mesangial cell proliferation.

Adoptive Transfer↗
PubMed2006

Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation.

During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus-specific donor T cells for adoptive transfer of immunity to patients with HAdV-infection/reactivation. Virus-specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN-gamma) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were infused for adoptive transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV-specific immunity was successful in five of six evaluable patients, documented by a dose-independent and sustained in vivo expansion of HAdV-specific T cells, associated with a durable clearance/decrease of viral copies. T-cell infusion was well tolerated in all nine patients, except one case with graft-versus-host disease II of the skin. In conclusion, induction of a specific T-cell response through adoptive transfer was feasible and effective. When performed early in the course of infection, adoptive T-cell transfer may protect from HAdV-related complications.

Adenovirus Infections, Human↗
PubMed1975

Suppression of reaginic antibody formation. II. The use of adoptive transfer system for the study of immunological unresponsiveness.

By the use of the adoptive transfer system in syngeneic mice it was demonstrated that: i) spleen cells of animals tolerized by the i.v. injection of DNP8-MgammaG 1 month before adoptive transfer into x-irradiated recipients remained unresponsive when further challenged with the sensitizing antigen (DNP2.3-OA administered i.p. with Al (OH)3); by contrast, a significant response (typical of a secondary response) was obtained in recipients of cells from mice which had received only the sensitized antigen; ii) the anti-hapten IgE secondary response of primed cells was not affected by the presence of cells of tolerized mice when these two types of cells were administered and challenged together in x-irradiated recipients; iii) the transfer of spleen cells or serum of mice, tolerized 20 days before harvesting, into intact syngeneic recipients did not interfere with the normal development of the anti-DNP IgE response of the latter; iv) the anti-hapten responses of tolerized animals receiving spleen cells from normal or primed mice together with the sensitizing antigen resulted, respectively, in a primary or secondary response; (v) the unresponsive state of tolerized cells, achievkd by immunosuppression of the original donors with respect to the haptenic determinant, was maintained even after two serial exposures of the cells to the immunizing antigen in two consecutive adoptive cell transfers into x-irradiated recipients. These findings provide a strong basis for the interpretation that the hapten-specific tolerace induced in mice by treatment with DNP8-MphiG involved the elimination or inactivation of hapten-specific IgE-producing cells or the blockade of the receptors of these cells.

Animals↗
PubMed1983

Adoptive transfer of delayed wattle reactivity in chickens with a dialyzable leukocyte extract containing transfer factor.

Delayed wattle reactions (DWR) to tuberculin, diphtheria toxoid (DT), and keyhole limpet hemocyanin (KLH) were transferred to chickens with dialyzable leukocyte extracts (DLE) prepared from splenic leukocytes of chickens sensitized and reactive by DWR to the tuberculin, DT, or KLH. A DLE prepared from chickens unsensitized and unreactive to tuberculin by DWR failed to transfer DWR to tuberculin in recipients. Only chickens injected with DLE from tuberculin sensitized and reactive chickens exhibited significant (P less than .01) DWR to tuberculin. Chickens that received DLE prepared from DT sensitized and reactive chickens exhibited significant (P less than .01) DWR to DT but not to KLH. Further, DWR to both DT and KLH was transferred with DLE prepared from chickens sensitized to both antigens. Adoptive transfer of DWR to KLH in comparison to DT was more successful. Finally, the serial transfer of DWR to KLH (P less than .05) but not to DT (P greater than .05) was accomplished using DLE prepared from chickens that previously were recipients of DLE prepared from chickens sensitized to KLH and DT. Results indicate that DLE prepared from chickens contain transfer factor (TF) responsible for adoptive transfer of DWR to tuberculin, DT, and KLH.

Animals↗
PubMed2005

Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer.

Transforming growth factor (TGF)-beta is a potent immunosuppressant. Overproduction of TGF-beta by tumor cells may lead to tumor evasion from the host immune surveillance and tumor progression. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. The mouse TRAMP-C2 prostate cancer cells produced large amounts of TGF-beta1 and were used as an experimental model. C57BL/6 mice were primed with irradiated TRAMP-C2 cells. CD8+ T cells were isolated from the spleen of primed animals, were expanded ex vivo, and were rendered TGF-beta insensitive by infecting with a retrovirus containing dominant-negative TGF-beta type II receptor. Results of in vitro cytotoxic assay revealed that these CD8+ T cells showed a specific and robust tumor-killing activity against TRAMP-C2 cells but were ineffective against an irrelevant tumor line, B16-F10. To determine the in vivo antitumor activity, recipient mice were challenged with a single injection of TRAMP-C2 cells for a period up to 21 days before adoptive transfer of CD8+ T cells was done. Pulmonary metastasis was either eliminated or significantly reduced in the group receiving adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells. Results of immunofluorescent studies showed that only tumor-reactive TGF-beta-insensitive CD8+ T cells were able to infiltrate into the tumor and mediate apoptosis in tumor cells. Furthermore, transferred tumor-reactive TGF-beta-insensitive CD8+ T cells were able to persist in tumor-bearing hosts but declined in tumor-free animals. These results suggest that adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for cancer therapy.

Adoptive Transfer↗
PubMedDate not supplied

A new model of chronic colitis in SCID mice induced by adoptive transfer of CD62L+ CD4+ T cells: insights into the regulatory role of interleukin-6 on apoptosis.

OBJECTIVE: The proinflammatory cytokine interleukin (IL)-6 is involved in various chronic inflammatory processes. IL-6 is a predominant cytokine produced by lamina propria T cells in Crohn's disease and experimental colitis. This study was designed to examine the effect of a neutralizing IL-6-receptor (IL-6R) antibody on the programmed cell death of mucosal T cells in the CD62L+ CD4+ SCID transfer model of chronic experimental colitis in mice and to gain more insight into the pathogenesis of this transfer colitis model. METHODS: For adoptive transfer, we isolated CD62L+ CD4+ double-positive T cells from wild-type BALB/c mice followed by intraperitoneal application of 1 million cells in CB17 SCID mice. The purity of the transferred T-cell population was tested by FACS analysis. Cytokine secretion was measured by ELISA. Western blot analysis was performed to detect phospho-STAT-3 in protein extracts of splenic cells. Cryo- and paraffin colon cross-sections were used to perform immunochemical or fluorescence TUNEL stainings. RESULTS: We isolated CD62L+ CD4+ and CD62L- CD4+ T cells. In vitro studies showed an increased production of IL-4 by CD62L- CD4+ T cells compared to CD62L+ T cells. 8-10 weeks after transfer of CD62L+ CD4+ T cells in SCID mice, reconstituted mice developed wasting disease, anal prolapse and diarrhea, whereas mice reconstituted with CD62L- CD4+ did not, similar to anti-IL-6R-treated CD62L+ CD4+-reconstituted SCID mice. Anti-IL-6R-treated reconstituted SCID mice showed decreased levels of activated STAT-3. The previously described efficacy of anti-IL-6R antibody treatment on colitis activity appeared to be due to the induction of apoptosis, as many TUNEL-positive cells were detected in the lamina propria. CONCLUSIONS: These results suggest that the activation of the IL-6/STAT-3-signaling pathway plays a pivotal role in the pathogenesis of CD62L+ CD4+ transfer colitis. Moreover, the application of a neutralizing antibody to IL-6R induces apoptosis in transferred T cells. These data implicate the importance of anti-apoptotic pathways in chronic disease and might contribute to future therapies.

Adoptive Transfer↗
PubMed1973

Hapten-specific IgE antibody responses in mice. II. Cooperative interactions between adoptively transferred T and B lymphocytes in the development of IgE response.

The present studies have established conditions for the demonstration of cooperative interactions between specific T and B lymphocyte populations in the development of IgE antibody responses in vivo in mice. This has been accomplished by utilizing a system which permits the successful adoptive transfer to irradiated recipients of DNP-specific secondary IgE responses with spleen cells from suitably primed syngeneic donor mice. Thus, adoptively transferred DNP-KLH or DNP-ASC-primed spleen cells produced high levels of anti-DNP antibodies of both IgE and IgG antibody classes in response to challenge with the appropriate homologous priming conjugate but failed to develop more than meager responses to the reciprocal heterologous conjugate. However, when spleen cells from donors primed to the second carrier were concomitantly transferred with hapten-primed lymphocytes, secondary IgE ant-DNP responses were consistently obtained upon challenge with the heterologous conjugate. Moreover, we have been able to elicit augmented primary IgE anti-DNP antibody responses to either DNP-ASC or DNP-KLH after adoptive transfer of spleen cells from donors primed only to the carrier, ASC or KLH, respectively. This adoptive transfer system has enabled us to provide direct proof for the participation of theta-bearing T lymphocytes in antibody responses of the IgE class. Thus, the capacity of ASC-primed spleen cells to effectively cooperate with the DNP-KLH-primed lymphocytes in the adoptive secondary response to DNP-ASC could be abolished by in vitro treatment of such cells with anti-theta serum plus complement. This was true not only for the anti-DNP response of the IgG antibody class, but for the IgE antibody class as well. These studies have, furthermore, demonstrated the capacity to stimulate secondary anti-DNP antibody production in vivo by the concomitant administration of the DNP and relevant carrier determinants on separate molecules. This was more readily seen in the IgE than in the IgG antibody class. Thus, DNP-ASC-primed cells developed significant IgE, but more variable IgG, anti-DNP responses upon challenge with DNP-KLH plus unconjugated ASC. Antibody responses of both classes elicited in this manner were appreciably improved by the transfer of additional carrier (ASC)-primed cells. These and other results presented herein suggest that IgE B lymphocyte precursors may be inherently more sensitive than IgG B cells to at least certain of the functions of T lymphocytes concerned with regulatory mechanisms involved in antibody production.

Adjuvants, Immunologic↗
PubMed1997

[Biotherapeutic efficacy of adoptive transfer of CD3AK cells in combination with cyclophosphamide and kappa-selenocarrageenan in P 388 leukemic mice].

OBJECTIVE: To study the antileukemia efficacy of a combination of adoptive transfer of CD3AK cells, cyclophosphamide (CTX), and kappa-selenocarrageenan (KSC) in P 388 leukemic mice. METHODS: CD3AK cells in normal DBA/2 murine splenocytes were induced with anti-CD3 antibody and low dose recombinant interleukin-2 (rIL-2). The P 388 murine leukemia model was induced by i.p. injection of P 388 cells into normal DBA/2 mice. The tumor-bearing mice were administrated with adoptively transferred CD3AK Cells and/or CTX and/or KSC. RESULTS: After tumor inoculation, the cellular immune function of P 388-bearing mice was supressed markedly. Adoptive transfer of CD3AK cells with low dose rIL-2 into the P 388 mice significantly enhanced the splenocyte proliferation (SP) induced by Con A, the NK cell activity and the splenocytic IL-2 production and prolonged their survival (45.19%); CTX (200 mg/kg) alone prolonged the survival of P 388-bearing mice (29.90%), but further decreased the immunodeficiency; combination of CTX and CD3AK passive transfer could prevent the reduction of SP, NK activity and IL-2 production in the leukemic mice and prolonged the survival (59.45%), combination of KSC and adoptively transfected CD2AK cells and/or CTX had a much better therapeutic efficacy for P 388 murine leukemia, 12.50%-75.00% of the leukemic mice were cured. CONCLUSION: KSC is a hopeful biological response modifier in cancer biotherapy, and tumor killing effector cells and chemotherapy plus BRM might be a promising candidate for human leukemia biotherapy.

Adoptive Transfer↗
PubMed2000

Tumor size at the time of adoptive transfer determines whether tumor rejection occurs.

Here we investigate the minimal requirements for induction of an anti-tumor response in CD8 T cells in vivo. We compare the efficacy of adoptive transfer of CD8 T cells with a transgenic TCR specific for the main cytotoxic T lymphocyte epitope of the influenza virus nucleoprotein (NP) on the growth of NP-expressing EL4 tumors under different conditions. In a setting in which tumor rejection is solely dependent on tumor-specific CD8 T cells, small immunogenic tumors fail to induce a rejection response, despite the fact that they are not ignored: tumor-specific CD8 T cells are activated, differentiate into effector cells and infiltrate the tumor bed. Nevertheless, tumor rejection does not occur. In sharp contrast, the same immunogenic tumor, when growing as a large tumor mass, is rejected by transferred tumor-specific CD8 T cells. The main features which distinguish the rejection response to a large tumor mass from the response to a small tumor is that, in the latter case, activated CD8 T cells appear much later, and in much smaller numbers. Efficacy of adoptive transfer is thus dictated by the size of the tumor mass at the time of transfer. These findings predict that treatment of minimal residual disease with adoptive transfer will fail, unless vaccination is also provided at the time of transfer.

Adoptive Transfer↗
PubMed2000

The effects of TCDD on the activation of ovalbumin (OVA)-specific DO11.10 transgenic CD4(+) T cells in adoptively transferred mice.

Exposure to the environmental contaminant 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses the generation of T cell-dependent immunity, both humoral and cell-mediated. However, the mechanism of TCDD-induced immune suppression remains to be defined. We hypothesized that exposure to TCDD suppresses the activation of naive CD4(+) T cells and prevents their expansion and differentiation into effector T-helper cells capable of driving T cell-dependent immune responses. To test this hypothesis, we adoptively-transferred DO11.10 OVA-specific T-cell receptor (TCR) transgenic T cells into syngeneic recipients and used a TCR-specific monoclonal antibody to track the in vivo activation of naive CD4(+) T lymphocytes following exposure to OVA. The production of OVA-specific antibodies was suppressed in a dose-dependent manner in adoptively transferred mice that had been exposed to TCDD. Although TCDD exposure had little effect on the expansion or activation of the adoptively transferred, OVA-specific CD4(+) T cells, these cells disappeared from the spleen more rapidly in TCDD-treated mice and produced significantly decreased levels of the T cell-derived cytokines IL-2 and IL-10. There was also a trend towards reduced IFN-gamma and IL-4 production following in vitro re-stimulation. These data suggest that TCDD may interfere with the survival and/or differentiation of OVA-specific T-helper cells. These results demonstrate for the first time the potential of the DO11.10 adoptive transfer system to directly assess immunotoxic effects of xenobiotics on antigen-specific CD4(+) T cells in vivo.

Adoptive Transfer↗
PubMed1998

Characteristics of tumor infiltration by adoptively transferred and endogenous natural-killer cells in a syngeneic rat model: implications for the mechanism behind anti-tumor responses.

Interleukin-2-activated, cultured NK cells (A-NK) cells were adoptively transferred into a syngeneic rat liver-tumor model. The kinetics of tumor infiltration by NK cells, originating either from adoptively transferred or from endogenous sources, the localization of these cells in the tumor, and their interactions with extracellular-matrix proteins were studied by immunohistochemistry and transmission-electron microscopy. The adoptive transfer of A-NK cells via the hepatic artery and s.c. injections of IL-2 into rats bearing subcapsularly induced CC531 liver tumors, but also IL-2 monotherapy, resulted in a significant increase of the number of NK cells both at the tumor border and in the tumor center. The majority of tumor-infiltrating NK cells was present in the tumor stroma and only occasionally was an NK cell observed in a tumor nodule in direct contact with tumor cells. Observations by electron microscopy suggested that matrix proteins, abundantly present in the tumor stroma but absent in the tumor nodules, provide a substrate for migration of infiltrating cells, whereas tight structures of matrix proteins surrounding tumor nodules provide a barrier for establishment of direct NK-cell-to-tumor-cell-contact. Our results suggest that direct NK-cell-to-target-cell-contact-mediated lysis is of minor importance for attaining an anti-tumor effect in this model. We hypothesize that treatment of tumor-bearing rats with A-NK cells and/or IL-2 initiates a cascade of events (e.g., secretion of tumor-killing cytokines and/or infiltration of other immune cells) ultimately leading to tumor regression.

Adoptive Transfer↗
PubMed1994

Adoptive transfer of experimental hypersensitivity pneumonitis: CD4+ cells are memory and naive cells.

We previously demonstrated that CD4+ cells are responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis. To further characterize the CD4+ cells as naive or memory cells, we depleted Micropolyspora faeni-sensitized cultured C3H/HeJ spleen cells of surface IgM+ cells by panning and Ia+ cells by lysis. We measured the proportion of CD4+ cells that expressed CD45RB, CD44 or LECAM-1 (markers used to distinguish memory from naive CD4+ cells) in spleen cell populations able to transfer experimental hypersensitivity pneumonitis (M. faeni sensitized and cultured) and those unable to transfer experimental hypersensitivity pneumonitis (ovalbumin sensitized and M. faeni cultured). Planning reduced the proportion of B cells from 53% to 11% and of Ia+ cells from 54% to 11%. Further lysis of Ia+ cells from the SIgM(+)-depleted population reduced Ia+ cells to 6%. Thy1+ cells increased from 26% to 55% after panning and to 72% after Ia+ cell lysis. Cultured M. faeni-sensitized spleen cells could transfer experimental hypersensitivity pneumonitis. Depletion of SIgM+ cells enhanced and depletion of Ia+ cells did not affect the capacity to transfer experimental hypersensitivity pneumonitis. The CD4+ cells from M. faeni-sensitized animals were 47% CD45RBhi, 36% CD44+ and 0% LECAM-1hi before culture with M. faeni and 48% CD45RBhi. They were 34% CD44+ and 27% LECAM-1hi after culture. The origin of the cells (from M. faeni- or ovalbumin-sensitized animals) did not affect the phenotype of the CD4+ cells, either before or after culture with M. faeni. We conclude that the active cells in spleen cell cultures are SIgM-, Ia-, CD4+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

A mouse model of pemphigus vulgaris by adoptive transfer of naive splenocytes from desmoglein 3 knockout mice.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by antidesmoglein3 (anti-Dsg3) IgG autoantibodies. Recently, we developed a PV mouse model by adoptive transfer of splenocytes from recombinant Dsg3-immunized Dsg3(-/-) mice to Rag2(-/-) immunodeficient mice that expressed Dsg3. OBJECTIVES: We determined whether the adoptive transfer of naive splenocytes from nonimmunized Dsg3(-/-) mice induces the anti-Dsg3 IgG production and the PV phenoytpe in recipient mice. METHODS: We adoptively transferred naive Dsg3(-/-) splenocytes into Rag2(-/-) mice and compared their PV phenoytpe with those mice receiving immunized Dsg3(-/-) splenocytes. The numbers of splenocytes and their subpopulations required for anti-Dsg3 IgG production were examined. RESULTS: Mice that received naive Dsg3(-/-) splenocytes produced anti-Dsg3 IgG, which bound to keratinocyte cell surfaces in vivo, and developed the PV phenotype, including oral erosions with suprabasilar acantholysis. Antibody production and the appearance of the PV phenotype were delayed by approximately 2 weeks in mice that received naive splenocytes compared with mice that received immunized splenocytes. However, once the PV phenotypes developed, there were no apparent differences in disease severity between the two models. Interestingly, the anti-Dsg3 IgG titres were significantly lower in mice that received naive splenocytes than in mice that received immunized splenocytes, suggesting that the former antibodies were more potent than the latter. The frequency of anti-Dsg3 IgG production depended on the number of transferred naive splenocytes. Both CD4+ T cells and B220+ B cells from naive Dsg3(-/-) mice were essential for the production of anti-Dsg3 IgG antibodies. CONCLUSIONS: Dsg3-specific naive lymphocytes in Dsg3(-/-) mice can be primed and activated by the endogenous Dsg3 in recipient mice to produce pathogenic anti-Dsg3 IgG without active immunization. This approach using naive lymphocytes provides a unique model to dissect immunological mechanisms of tolerance against peripheral autoimmune targets.

Adoptive Transfer↗
PubMed1995

Adoptive transfer of T lymphocytes to T-cell-depleted mice inhibits Escherichia coli translocation from the gastrointestinal tract.

Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal (GI) tract to extraintestinal sites, such as the mesenteric lymph node (MLN), spleen, liver, kidneys, and blood. Previously, we reported that depletion of CD4+ and/or CD8+ T cells promotes bacterial translocation from the GI tract to the MLN. In the present study, CD4+ and/or CD8+ T cells, harvested from donor mice, were adoptively transferred to mice previously depleted of T cells by thymectomy plus intraperitoneal injection of rat anti-mouse T-cell monoclonal antibodies. The adoptively transferred CD4+ and/or CD8+ T cells inhibited the translocation of Escherichia coli from the GI tract. Migration of the adoptively transferred T cells to the spleens and MLNs of the recipient mice was determined by utilizing Thy 1.1+ donor cells adoptively transferred into mice whose cells express the Thy 1.2 marker. These results provide further evidence of the importance of T cells in the host immune defense against bacterial translocation from the GI tract.

Animals↗