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PubMed2006

Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation.

Immunoincompetence after allogeneic hematopoietic stem cell transplantation (HSCT) affects in particular the T-cell lineage and is associated with an increased risk for infections, graft failure and malignant relapse. To generate large numbers of T-cell precursors for adoptive therapy, we cultured mouse hematopoietic stem cells (HSCs) in vitro on OP9 mouse stromal cells expressing the Notch-1 ligand Delta-like-1 (OP9-DL1). We infused these cells, together with T-cell-depleted mouse bone marrow or purified HSCs, into lethally irradiated allogeneic recipients and determined their effect on T-cell reconstitution after transplantation. Recipients of OP9-DL1-derived T-cell precursors showed increased thymic cellularity and substantially improved donor T-cell chimerism (versus recipients of bone marrow or HSCs only). OP9-DL1-derived T-cell precursors gave rise to host-tolerant CD4+ and CD8+ populations with normal T-cell antigen receptor repertoires, cytokine secretion and proliferative responses to antigen. Administration of OP9-DL1-derived T-cell precursors increased resistance to infection with Listeria monocytogenes and mediated significant graft-versus-tumor (GVT) activity but not graft-versus-host disease (GVHD). We conclude that the adoptive transfer of OP9-DL1-derived T-cell precursors markedly enhances T-cell reconstitution after transplantation, resulting in GVT activity without GVHD.

Adoptive Transfer↗
PubMed1977

Adoptive transfer of immunity from mice immunized with ribosomes or live yeast cells of Histoplasma capsulatum.

This investigation was designed to compare the role of lymphoid cells and immune serum in protective immunity induced by immunization with ribosomes or live yeast cells of Histoplasma capsulatum. Spleen cells, peritoneal cells, and serum from C3H mice immunized with Histoplasma ribosomes or live cells were transferred intravenously to separate groups of syngeneic recipients. All recipients along with a set of immunized and control mice were challenged intravenously with 4 x 10(6) yeast cells of H. capsulatum, and protection was assessed. Immunization with ribosomes or live cells provided 90 to 100% protection. Mice receiving filtered spleen cells or peritoneal cells from donors immunnized with live cells showed 90 to 100% protection; 80 to 90% protection was observed for mice receiving cells from ribosome-immunized donors. In contrast, no evidence of protection was seen in mice receiving serum from either live-cell- or ribosome-immunized mice. Peritoneal cells were far more efficient than spleen cells in adoptive transfer of immunity. The adoptive immunity in recipients persisted for at least 3 weeks after transfer, the longest period tested in the present study. These results indicate that the immunity elicited by immunization with Histoplasma ribosomes or live cells is mediated by a cellular mechanism.

Animals↗
PubMed2003

TNF plays an essential role in tumor regression after adoptive transfer of perforin/IFN-gamma double knockout effector T cells.

We have recently shown that effector T cells (T(E)) lacking either perforin or IFN-gamma are highly effective mediators of tumor regression. To rule out compensation by either mechanism, T(E) deficient in both perforin and IFN-gamma (perforin knockout (PKO)/IFN-gamma knockout (GKO)) were generated. The adoptive transfer of PKO/GKO T(E) mediated complete tumor regression and cured wild-type animals with established pulmonary metastases of the B16BL6-D5 (D5) melanoma cell line. PKO/GKO T(E) also mediated tumor regression in D5 tumor-bearing PKO, GKO, or PKO/GKO recipients, although in PKO/GKO recipients efficacy was reduced. PKO/GKO T(E) exhibited tumor-specific TNF-alpha production and cytotoxicity in a 24-h assay, which was blocked by the soluble TNFRII-human IgG fusion protein (TNFRII:Fc). Blocking TNF in vivo by administering soluble TNFR II fusion protein (TNFRII:Fc) significantly reduced the therapeutic efficacy of PKO/GKO, but not wild-type T(E). This study identifies perforin, IFN-gamma, and TNF as a critical triad of effector molecules that characterize therapeutic antitumor T cells. These insights could be used to monitor and potentially tune the immune response to cancer vaccines.

Adoptive Transfer↗
PubMedDate not supplied

Targeting tumours by adoptive transfer of immune cells.

1. Surgery, radiotherapy and chemotherapy are the most widely used and well-established modalities for treating malignant diseases. Surgery is used to excise solid tumours and radiotherapy/chemotherapy are used for the treatment of liquid tumours and for solid tumours where there is a risk of micrometastases. A major drawback for both radiotherapy and chemotherapy is their lack of specificity for tumour cells. Both these treatments can destroy normal bone marrow cells and result in severe side-effects. 2. The impairment of haemapoiesis due to bone marrow destruction combined with the use of toxins in chemotherapy that inhibit the proliferation of immune cells leaves many patients immunocompromised. This complicates the development of prophylactic (vaccine) strategies for tumours where patients are undergoing conventional therapy. 3. An alternative approach is to expand and activate tumour-specific immune cells in vitro that can then be adoptively transferred back in large numbers. This is defined as adoptive immunotherapy and has the advantage of potentially bypassing the immuno-inhibitory effects of conventional therapies. 4. Transferred immune cells have been shown to mediate tumour regression in patients by both direct and indirect mechanisms. The immune cells used include tumour reactive T lymphocytes and dendritic cells, which elicit tumour specific responses. 5. Many novel cell-based immunotherapeutic strategies developed in murine tumour models are now being applied in human clinical trials. The malignancies targeted include melanoma, chronic myelogenous leukaemia and breast, ovarian, colon and kidney cancers. In the present review, we discuss these novel cell-based strategies and the implications they have for the future treatment of human malignancies.

Adoptive Transfer↗
PubMed1996

Influence of interleukin-2 regimens on circulating populations of lymphocytes after adoptive transfer of anti-CD3-stimulated T cells: results from a phase I trial in cancer patients.

The adoptive transfer of anti-CD3-stimulated T killer (T-AK) cells was tested with different bolus and infusional interleukin-2 (IL-2) regimens, and anti-CD3 stimulation procedures to determine immunologic and antitumor effects in patients with a variety of advanced cancers. Indium-111 labeling was used to observe traffic patterns of the infused T-AK. Autologous peripheral blood mononuclear cells were obtained by leukapheresis. Cyclophosphamide (300 mg/m2) was given to most patients immediately after leukapheresis. The harvested cells were activated ex vivo with anti-CD3 overnight or for 4 days, at which time cells were reinfused and an IL-2 regimen was begun. Treatment was repeated 28 days later. This treatment regimen induced significant increases in leukocytes, lymphocytes, and eosinophils in patients in most treatment cohorts. Circulating lymphocytes were predominantly CD3+ T cells with preferential expansion of the CD8+ subset. Patients receiving cells stimulated in vitro for 4 days had significant T-cell lymphocytosis with either infusional or bolus plus infusional IL-2 regimens. T-cell viability was decreased in culture after a second 4-day stimulation with anti-CD3 at day 28; this decrease could be prevented by adding IL-2 to the culture media. Cells stimulated overnight required both bolus and infusional IL-2 to show an atypical lymphocytosis in vivo. Overnight-stimulated T-AK did not show decreases in in vitro viability at the day 28 restimulation. Indium-III-labeled cells trafficked to the liver, spleen, and bone marrow. No increase in uptake was observed in tumor deposits. There were 2 patients with partial responses, 5 with minor responses, 19 with stable disease, and 88 with progressive disease. The length of in vitro anti-CD3 stimulation, and the dose and timing of IL-2 administration in vivo results in different circulating leukocyte populations after adoptive T-AK infusion. Generally, the CD8+ T-cell subset was preferentially expanded by this treatment approach. Repeated ex vivo stimulation with anti-CD3 may cause cell death.

Adolescent↗
PubMed1999

IL-4-transduced tumor cell vaccine induces immunoregulatory type 2 CD8 T lymphocytes that cure lung metastases upon adoptive transfer.

Vaccinations with tumor cells engineered to produce IL-4 prolonged survival and cured 30% of mice bearing pulmonary metastases, an effect abrogated by in vivo depletion of T cells. Vaccination induced type 2 T cell polarization in both CD4 and CD8 T lymphocyte subsets. We focused on the antitumor activity exerted by type 2 CD8+ T cells (Tc2) activated by IL-4 tumor cell vaccination. Tc2 lymphocytes lacked in vitro tumor cytotoxicity, but released IL-4 upon stimulation with tumor cells, as shown by limiting dilution analysis of the frequencies of tumor-specific pCTL and of CD8 cells producing the cytokine. In vivo fresh purified CD8+ T lymphocytes from IL-4-vaccinated mice eliminated 80-100% of lung metastases when transferred into tumor-bearing mice. CD8+ lymphocytes from IL-4-vaccinated IFN-gamma knockout (KO), but not from IL-4 KO, mice cured lung metastases, thus indicating that IL-4 produced by Tc2 cells was instrumental for tumor rejection. The antitumor effect of adoptively transferred Tc2 lymphocytes needed host CD8 T cells and AsGM1 leukocyte populations, and partially granulocytes. These data indicate that Tc2 CD8+ T cells exert immunoregulatory functions and induce tumor rejection through the cooperation of bystander lymphoid effector cells. Tumor eradication is thus not restricted to a type 1 response, but can also be mediated by a type 2 biased T cell response.

Adoptive Transfer↗
PubMed2003

Relationship between beta cell mass of NOD donors and diabetes development of NOD-scid recipients in adoptive transfer system.

BACKGROUND: There is controversy about the way the beta cell mass is reduced in type 1 diabetes. One view is that a gradual fall in beta cell mass begins soon after the onset of insulitis. Another view is that a sudden wave of beta cell destruction occurs just before the onset of diabetes. To clarify how the beta cell mass is reduced, we performed adoptive transfer experiments and examined the relationship between the pancreatic status of NOD donors and the time taken to transfer diabetes into NOD-scid recipients. METHODS: We killed 18-week-old female NOD mice (n = 20), removed their spleen, and transferred splenocytes into 5-week-old female NOD-scid mice (n = 60). The relationship between the pancreatic status of donors and the time taken to transfer diabetes into recipients was assessed. As pancreatic status, we measured insulin content and severity of insulitis. RESULTS: There was no linear correlation between the pancreatic status of donors and the time taken to transfer diabetes into recipients. NOD donors who needed 7 or more weeks to transfer diabetes in NOD-scid recipients had similar levels of insulin content or severity of insulitis as those of NOD donors who could not transfer diabetes. On the other hand, NOD donors who needed 6 or less weeks to transfer diabetes in recipients had similar levels of insulin content or severity of insulitis as those of diabetic NOD mice. CONCLUSIONS: According to our observations, beta cell mass seems to be preserved until just before the onset of diabetes and decreased dramatically within a few weeks.

Adoptive Transfer↗
PubMed1998

Systemic complement depletion reduces inflammation and demyelination in adoptive transfer experimental allergic neuritis.

The effect of systemic complement depletion by cobra venom factor (CVF) was evaluated in adoptive transfer experimental allergic neuritis (AT-EAN). Spleen cells of rats immunized with a neuritogenic peptide SP26 were injected into naive rats. On days 3 and 6 after cell transfer AT-EAN rats were treated with CVF or saline intraperitoneally. AT-EAN rats treated with CVF had significantly lower scores for histological inflammation (0.25 +/- 0.25 vs 1.9 +/- 0.4, mean +/- SEM, P < 0.03) and demyelination (0.13 +/- 0.13 vs 1.6 +/- 1.4, P < 0.02) than saline-treated AT-EAN rats. Immunocytochemistry of lumbosacral nerve roots showed significantly less ED1-positive macrophages (0.5 +/- 0.3 vs 1.6 +/- 0.6, P < 0.04) and CD11bc-positive (expressing complement receptor 3 or CR3) inflammatory cells (0.6 +/- 0.4 vs 1.7 +/- 0.5, P < 0.03). Our data suggest that complement plays a crucial role in inflammatory demyelination since systemic complement depletion significantly reduces recruitment of macrophages into the nerve and subsequent macrophage-mediated demyelination.

Animals↗
PubMed1980

Genetic control of immunity to parasites: adoptive transfer of immunity between inbred strains of mice characterized by rapid and slow immune expulsion of Trichinella spiralis.

Adoptive transfer of immunity with immune mesenteric lymph node cells (IMLNC) was used to analyse the roles of immune and inflammatory events in determining the strain-characteristic time of expulsion of Trichinella spiralis from mice. Transfer of IMLNC within and between three rapidly responding strains (NIH, SWR, DBA1-all H-2q) resulted in accelerated worm expulsion, worm loss commencing before day 8 in each case. When NIH cells were transferred to slow-responder B10 congenic mice (B10G-H-2q) mice, immunity was evident at 8 days as a reduction in worm fecundity and only by 12 days as a reduction in worm numbers. A similar result was obtained when B10G cells were given to B10G recipients. In the reciprocal transfer, IMLNC from B10G transferred immunity to NIH as effectively and as rapidly as did NIH cells. Cells capable of transferring immunity were present in B10G mice as early as 4 days after infection, even though worm expulsion in this strain does not occur until after day 12. Thus following heterologous transfers of IMLNC, the time of worm expulsion was determined by the response of the recipient, and presumably by the ability to generate intestinal inflammatory changes. Earlier work has shown that the strain-characteristic time of worm expulsion is genetically determined, but not by H-2 linked genes. A corollary of the present work is that non-H-2 linked genes control the generation of intestinal inflammatory changes in T. spiralis infections. H-2 genes may control lymphocyte responsiveness to infection and the haplotype H-2q may determine a rapid response. Comparisons are made with the genetic control of resistance to Listeria monocytogenes and possible mechanisms are discussed.

Animals↗
PubMed2004

Antineuroinflammatory effect of NF-kappaB essential modifier-binding domain peptides in the adoptive transfer model of experimental allergic encephalomyelitis.

It has been shown that peptides corresponding to the NF-kappaB essential modifier-binding domain (NBD) of IkappaB kinase alpha or IkappaB kinase beta specifically inhibit the induction of NF-kappaB activation without inhibiting the basal NF-kappaB activity. The present study demonstrates the effectiveness of NBD peptides in inhibiting the disease process in adoptively transferred experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis. Clinical symptoms of EAE were much lower in mice receiving wild-type (wt)NBD peptides compared with those receiving mutated (m)NBD peptides. Histological and immunocytochemical analysis showed that wtNBD peptides inhibited EAE-induced spinal cord mononuclear cell invasion and normalized p65 (the RelA subunit of NF-kappaB) expression within the spinal cord. Analysis of lymph node cells isolated from donor and recipient mice showed that wtNBD peptides but not mNBD peptides were able to shift the immune response from a Th1 to a Th2 profile. Consistently, wtNBD peptides but not mNBD peptides inhibited the encephalitogenicity of myelin basic protein-specific T cells. Furthermore, i.p. injection of wtNBD peptides but not mNBD peptides was also able to reduce LPS- and IFN-gamma-induced expression of inducible NO synthase, IL-1beta, and TNF-alpha in vivo in the cerebellum. Taken together, our results support the conclusion that NBD peptides are antineuroinflammatory, and that NBD peptides may have therapeutic effect in neuroinflammatory disorders such as multiple sclerosis.

Adoptive Transfer↗
PubMed2004

Generation, maintenance, and adoptive transfer of diabetogenic T-cell lines/clones from the nonobese diabetic mouse.

The ability to generate, maintain, and use cloned lines of T cells reactive for self-antigens has opened up a new avenue of investigation for researchers. These T-cell clones allow the rapid induction of tissue-specific autoimmunity with the intent of dissecting the contribution of the different cell types involved. T cells from the diabetes-prone nonobese diabetic mouse are proving to be a vital asset for understanding the T-cell-mediated pathogenesis that leads to overt beta-cell destruction. T-cell clone adoptive transfer protocols have been developed for use in immunodeficient strains, thus reducing the complexity of mechanism of disease initiation. Furthermore, these T-cell clones have been used to derive T-cell receptor transgenic (TCR-Tg) animals carrying only self-reactive T cells. The use of these TCR-Tg animals to study pathogenesis has also evolved from the ability to generate, maintain, and use T-cell cloned lines. This chapter focuses on primary culture for the generation of T-cell lines and clones, their long-term maintenance, and their use in disease transfer for studying the pathogenesis of end-organ autoimmunity.

Adoptive Transfer↗
PubMed1997

Inductive events in oral tolerance in the TCR transgenic adoptive transfer model.

Oral administration of antigen induces a systemic hyporesponsiveness termed oral tolerance. High doses of oral antigen lead to deletion or anergy of T-cells whereas low doses induce regulatory T-cells that secrete Th2 cytokines (IL-4/IL-10) and TGF-beta. The initiating events associated with oral tolerance have not been well characterized. We investigated the induction phase of oral tolerance by adoptively transferring ovalbulumin (OVA) p (323-339) TcR specific transgenic (Tg+) T-cells into BALB/c recipients that were then fed either a high (5 mg x 5) or a low (0.1 mg x 5) dose of OVA 323-329 peptide. The frequency of Tg+ T-cells in lymphoid tissues was determined by flow cytometry using an anti-clonotypic monoclonal antibody. In high-dose-fed animals, Tg+ cells increased six- to eightfold in Peyer's patches after one feeding and then progressively decreased to 44% of those in the control by Day 20. In contrast, a biphasic-type response was observed in lymph node and spleen where Tg+ cells decreased after the first feeding, returned to the control level, and then decreased to 36-63% of the control level by Day 20. In low-dose-fed animals, changes in Tg+ T cells were only observed in Peyer's patches after five feedings, where cells increased approximately twofold. T-cell activation as measured by proliferation and IFN-gamma secretion occurred in both low- and high-dose-fed animals after only one feeding and then declined whereas secretion of Th2 cytokines and TGF-beta remained high even 10 days after the last feeding in low-dose-fed animals. Immunization with OVA/CFA demonstrated peripheral tolerance as measured by decreased proliferation and IFN-gamma secretion and was associated with increased production of TGF-beta and IL-10. These results suggest that the inductive phase of oral tolerance is characterized by an activation of antigen-specific T-cells that involves the initial secretion of IFN-gamma followed by prolonged secretion of Th2 cytokines and TGF-beta.

Administration, Oral↗
PubMed2002

Accumulation of immunoglobulin across the 'blood-nerve barrier' in spinal roots in adoptive transfer experimental autoimmune neuritis.

At the onset of Guillain-Barré syndrome, disruption of diffusion barriers, such as the blood-nerve barrier, probably increases the exposure of spinal roots and peripheral nerves to macromolecules, some of which might be pathogenic. As a measure of such disruption, we measured the accumulation in the endoneurium of spinal roots and sciatic nerve of systemically administered 125I-labelled immunoglobulin in adoptive transfer experimental autoimmune neuritis (AT-EAN) in the rat. AT-EAN is a model of Guillain-Barré syndrome, induced by injection of activated T lymphocytes sensitized to myelin P2 protein. Immunoglobulin accumulation was expressed as counts/min/mg in fixative-perfused roots as a percentage of that in serum, measured 24 h after intraperitoneal injection of 0.1 micro Ci 125I-labelled immunoglobulin. Immunoglobulin accumulation in the roots of normal rats was 3 +/- 1% (mean +/- SE), but this first increased 3(1/2) days after cell injection, peaked at 22 +/- 2% on day 4(1/2), and declined to normal by day 8. T lymphocytes and polymorphonuclear leucocytes first appeared within the endoneurium at day 3(1/2), and macrophages and a few erythrocytes at day 4. Neurological deficit appeared on day 4 and was maximal on day 6. Demyelination and axonal degeneration began at day 5. The first abnormality detected in AT-EAN was a rapid increase in the passage of immunoglobulin into spinal roots, together with endoneurial infiltration of T lymphocytes and polymorphonuclear leucocytes. Accumulation of immunoglobulin was maximal during the worsening of neurological deficit, and declined rapidly before the onset of neurological recovery.

Adoptive Transfer↗
PubMed2005

Chronic allograft nephropathy in athymic nude rats after adoptive transfer of primed T lymphocytes.

The impact of presensitized T lymphocytes on the development of chronic allograft nephropathy (CAN) was investigated in nude athymic LEW.RNU recipients of F344 renal allografts. The recipients (n = 8) were reconstituted with 5 x 10(7) T lymphocytes primed against donor skin grafts to induce graft rejection. LEW.RNU (n = 8) and euthymic LEW recipients (n = 6) which underwent no further intervention after transplantation served as control groups. Adoptive transfer of primed T cells induced CAN in LEW.RNU rats. Their kidney function decreased progressively. After 90 days a moderate glomerulopathy, tubular atrophy and interstitial fibrosis were observed, vascular changes were only mild or absent. Cellular infiltrates were predominated by CD4+ T cells and ED1+ macrophages. Deposition of tenascin and laminin was enhanced. Grafts of euthymic recipients displayed only mild signs of CAN according to the Banff criteria. These data implicate an important role for the cellular immune response in the development of CAN.

Adoptive Transfer↗
PubMed2000

Adoptive transfer of beta(2)-glycoprotein I-reactive lymphocytes enhances early atherosclerosis in LDL receptor-deficient mice.

BACKGROUND: It has been proposed that autoimmune factors can influence the progression of atherosclerosis. We have previously shown that immunization of LDL receptor-deficient (LDL-RD mice) with beta(2)-glycoprotein I (beta2GPI; a principal target of "autoimmune" antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of beta2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice. METHODS AND RESULTS: LDL-RD mice were immunized with human beta2GPI. An additional group of mice were immunized with beta2GPI and boosted with the same antigen 3 weeks later. Control mice with immunized with human serum albumin. Lymphocytes obtained from the draining lymph node cells or from splenocytes of beta2GPI- or human serum albumin-immunized mice were stimulated in vitro with beta2GPI or with the mitogen concavalin A, respectively. The cultured lymphocytes were transferred intraperitoneally to syngenic LDL-RD mice, and the mice were fed a high-fat "Western" diet for 5 weeks until death. Mice injected with lymphocytes from draining lymph nodes or spleens of beta2GPI-immunized animals displayed larger fatty streaks than those induced by control treated animals. T-cell-depleted splenocytes from beta2GPI were unable to promote lesion formation in the mice. CONCLUSIONS: The present study provides the first direct evidence for a role of antigen (beta2GPI)-reactive T cells in the promotion of fatty streaks in mice.

Adoptive Transfer↗
PubMed2006

Adoptively transferred Th1 cell populations lose IFNgamma+ cells by cytokine down-regulation on single-cell level.

Against the background of effector T cell heterogenity in terms of their in situ cytokine expression, IFNgamma production has been argued to define distinct Th1 lineages: whereas IFNgamma- Th1 cells survive and differentiate in vivo, IFNgamma+ Th1 cells eventually undergo apoptosis. Alternatively, lineage commitment might not be directly associated with the actual IFNgamma production. To address this issue, we adoptively transferred in vitro-polarized Th1 cell populations. Although absolute numbers of total Th1 cells after 3 days in vivo remained unchanged, numbers of IFNgamma+ within the Th1 cells declined by approximately 50%. This was not affected by the initial frequencies of IFNgamma+ cells within the transferred Th1 cell populations and by the presence of the antigen. Arguing against positive selection of IFNgamma non-producers in vivo, cell division rates of IFNgamma+ and IFNgamma- Th1 cells were comparable. Our data suggest that the 'loss' of IFNgamma+ cells within the transferred Th1 cell population might be rather caused by down-regulation of the cytokine expression on single-cell level than by deletion of individual IFNgamma+ cells. Thus, our findings are more in line with the hypothesis that actual cytokine expression does not define distinct differentiation states and polarization-specific genes remain accessible also in IFNgamma- Th1 effector cells.

Adoptive Transfer↗
PubMed2006

TH1/TH2-mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T lymphocytes into nude mice.

BACKGROUND: Transfer of CD4CD45RB T cells from normal donors to SCID/Rag-1, 2-deficient mice, which lack T and B cells, leads to the development of a TH1-mediated inflammatory bowel disease (IBD)-like syndrome characterized by extensive mononuclear cell infiltrates and epithelial cell hyperplasia. Because it is well known that B cells are also involved in a multitude of mechanistic pathways in human IBD, this study attempts to establish a new model of colitis in nude mice. METHODS: We transferred CD4CD45RB T cells into athymic nude mice, which lack thymus-dependent T cells but retain normal B cells, to establish and investigate a B cell-involving chronic colitis model. As a control, CD4CD25 T cells were also used. RESULTS: Mice reconstituted with CD4CD45RB but not CD4CD25 T cells developed a wasting disease, with severe infiltrates of B cell aggregates as well as T cells, macrophages, and dendritic cells into the colon and elevated levels of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-4, IL-5, and IL-10, by 7 weeks after T cell transfer. Furthermore, the infiltrated lamina propria B cells in colitic nude mice consisted predominantly of massive aggregated immunoglobulin (Ig) M- and scattered IgG-positive cells, but not IgA-positive cells. In contrast, mice reconstituted with CD4CD45RB and CD4CD45RB did not develop wasting disease or colitis. CONCLUSIONS: Collectively, the power of the colitis model induced by the adoptive transfer of CD4CD45RB T cells into nude mice is that one can investigate the roles of TH2-type cells and B cells in a regulatory T cell-depleted condition.

Adoptive Transfer↗
PubMed2002

Organ-specific cytokine polarization induced by adoptive transfer of transgenic T cells.

There are two distinct phenotypes of T cell cytokine responses that lead to different effector functions and different outcomes in disease processes. Although evidence suggests a possible role of the local microenvironment in the differentiation or localization of T cells with these phenotypes, there are no examples of divergent T cell cytokine phenotypes with the same Ag specificity concurrently existing in different tissue compartments. Using a CD8(+) T cell adoptive transfer model for graft-vs-host disease, we demonstrate that a potent type 2 cytokine response develops in the spleen while a potent type 1 cytokine response simultaneously develops in the testis. These experiments demonstrate for the first time that cytokine production can be oppositely polarized in different organs of the same individual. This may have important implications for organ-specific pathology in infection or autoimmunity: infections or autoimmune diseases that affect multiple organs may have heterogeneity in tissue cytokine responses that is not revealed in systemic lymphocyte cytokine responses. Therefore, attempts to modulate the immune response phenotype may ameliorate pathology in one organ while exacerbating pathology in another.

Adoptive Transfer↗