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PubMed2000

Adoptive transfer of acute lung injury.

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.

Adoptive Transfer↗
PubMed1983

Role of contrasuppression in the adoptive transfer of immunity.

The data presented in this paper show that the population of cells that adoptively transfer contact hypersensitivity are Lyt-1+ 2-, I-J- and nonadherent to V. villosa lectin. However, the adoptive transfer of immunity by this population of cells is successful only when the recipient has been treated in such a way as to impair the host immunosuppression mechanism. This population cannot, on its own, transfer immunity to adult, untreated naive recipients unless an additional population of immunoregulatory cells is present. This immunoregulatory population does not itself adoptively transfer immunity. This latter population is differentiated from the immune cells in that they are Lyt-1+ 2-, I-J+ and are adherent to V. villosa lectin. Both populations are required to adoptively transfer immunity to adult untreated naive recipients.

Animals↗
PubMed1963

FURTHER STUDIES ON ADOPTIVE TRANSFER OF SENSITIVITY TO SKIN HOMOGRAFTS.

Mice or rats that have been rendered tolerant of skin homografts from an alien donor strain furnish the basis of a very sensitive and objective test system for investigating the competence of cellular inocula from specifically immunized isologous donors to transfer sensitivity adoptively. By means of this test system it has been shown that immunologically "activated" cells, capable of transferring homograft sensitivity, are present in the blood, peritoneal exudates, and regional nodes of animals that have rejected skin homografts. Leucocytes were as effective as regional node cells. Activated cells were first demonstrable in the regional nodes and blood of skin homograft recipients at the same time,-on the 6th postoperative day,-suggesting that these cells must enter the circulation very soon after their formation in the nodes. Moreover, when sensitization was effected by skin homografts, but not by means of splenic cell suspensions inoculated intraperitoneally, activated cells are highly persistent, still being demonstrable in both the blood and the nodes more than a year after sensitization. The finding that thoracic duct cells, which are almost exclusively lymphocytes, were just as effective as leucocytes or regional nodes in transferring sensitivity in rats formally identifies the cell type responsible for transferring sensitivity in the various tissues tested. Attempts to transfer sensitivity to homografts in normal mice or tolerant mice by means of larger dosages of activated lymphoid cells sequestered in Millipore chambers inserted intraperitoneally were unsuccessful. All this, and other evidence presented, lends strength to the thesis that skin homograft immunity is a cell-mediated reaction.

Adoptive Transfer↗
PubMed1999

Protection against murine cytomegalovirus retinitis by adoptive transfer of virus-specific CD8+ T cells.

PURPOSE: Human cytomegalovirus retinitis, the most common ophthalmic infection of AIDS patients, has been modeled in BALB/c mice infected with murine cytomegalovirus by the supraciliary route. A series of depletion and adoptive transfer studies was performed to determine whether adoptive transfer of T cells protects mice from retinitis caused by murine cytomegalovirus infection after supraciliary inoculation and to determine which subset of T cells is responsible for protection. METHODS: BALB/c mice were thymectomized and T cell-depleted by injection of monoclonal antibodies to CD4, CD8, or both. Murine cytomegalovirus (9 x 10(2) plaque forming units [pfu]) was injected into the supraciliary space. Experimental animals received murine cytomegalovirus-specific T cells or subsets of T cells 2 hours before virus injection, whereas control animals received herpes simplex virus type 1-specific T cells by tail vein injection. Eight days after virus injection, retinal pathology was scored by histopathologic examination of hematoxylin and eosin-stained ocular sections. RESULTS: CD8+ T cell depletion was sufficient for development of retinitis after supraciliary injection of murine cytomegalovirus. Adoptive transfer of murine cytomegalovirus-specific T cells, but not herpes simplex virus type 1-specific T cells, provided protection from retinitis. Additionally, separation of the murine cytomegalovirus-specific T cells into CD8+ and CD4+ subsets before adoptive transfer showed that the CD8+ fraction of the adoptive T cells was responsible for protection. CONCLUSIONS: These results suggest that adoptive transfer of cytomegalovirus-specific T cells or T cell subsets might be used to treat or prevent cytomegalovirus retinitis in immunosuppressed human patients.

Animals↗
PubMed2002

Distribution of adoptively transferred, tumor-sensitized lymphocytes in the glioma-bearing rat.

For adoptively transferred lymphocytes to exert anti-tumor effects in vivo, they must traffic or initiate the migration of endogenous immune cells to the site of tumor. Using a rat model, we examined the trafficking of tumor-sensitized lymphocytes to an intracerebral glioma. By labeling the cells with 111Indium oxine (111In) prior to intravenous injection, we were able to quantify the relative number of lymphocytes that traveled to the tumor site. There was no difference in lymphocytic influx between the tumor-bearing and non-tumor-bearing cerebral hemispheres in 3-day rat glioma models. However, in 7-day models, significantly greater numbers of 111In-labeled lymphocytes resided in the tumor-bearing hemisphere at 12 h post-administration. This number increased more than two-fold by 24 h post-adoptive transfer. Using fluorescent-labeled lymphocytes and microscopy, we confirmed that the detection of radioactivity within the brain was truly due to tumor infiltrating 111In-labeled lymphocytes. Adoptively transferred cells were found in perivascular and peritumoral locations. These data demonstrate that tumor-sensitized lymphocytes traffic to an intracerebral target site where they can exert an effect, further supporting adoptive immunotherapy as a treatment for glioma.

Adoptive Transfer↗
PubMed1990

Proteoglycan-induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice.

Mononuclear cells from BALB/c mice with progressive polyarthritis and spondylitis induced by injection of fetal human articular cartilage proteoglycan (PG) were used to transfer arthritis by intravenous injection into irradiated, nonimmunized syngeneic mice. Successful transfer of arthritis to BALB/c mice required the injection of lymphocytes from mice with arthritis, along with 50 micrograms of human fetal PG, or lymphocytes stimulated in vitro with either fetal human PG or with mouse cartilage PG. In addition, interleukin-2 or immune sera from animals with arthritis significantly reduced the time to onset of transferred disease. The onset of adoptively transferred arthritis, using cells and antigen, from the time of the first injection (38.2 +/- 18.2 days, mean +/- SD) was shortened if lymphocytes from mice with transferred arthritis were reinjected (retransferred) into other, irradiated syngeneic mice (6.1 +/- 2.6 days). The appearance of autoreactive antibodies to mouse cartilage PG in the sera of mice with adoptively transferred arthritis (secondary or tertiary) preceded the appearance of the first clinical symptoms by a few days. The transfer of arthritis was blocked by pretreatment of donor (arthritic) lymphocytes with either anti-T cell or anti-B cell antibodies and complement. Exposure of mononuclear cells from mice with arthritis to PG, and its removal prior to transfer, also resulted in transfer of the arthritis. PG-induced arthritis was not transferred to nonirradiated mice, nor to irradiated mice injected with lymphocytes from animals with primary arthritis without chondroitinase ABC-digested fetal human PG. Arthritis never developed after injection of immune sera from mice with arthritis (without cells), nor when cells of nonarthritic animals were used with chondroitinase ABC-digested fetal human PG, with or without interleukin-2.

Animals↗
PubMed1993

Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization.

Antigen-driven tolerance is an effective method of suppressing cell-mediated immune responses. We have previously shown that oral administration of myelin basic protein (MBP) suppresses experimental autoimmune encephalomyelitis (EAE) when it is actively induced by MBP emulsified in complete Freund's adjuvant. In order to further study antigen-driven tolerance in this model, we investigated the effect of oral tolerization on adoptively transferred EAE and compared oral tolerance to intravenously (i.v.) administered MBP in both actively induced EAE and adoptively transferred EAE. Although orally tolerized animals were not protected from adoptively transferred EAE, spleen cells from orally tolerized animals suppressed adoptively transferred EAE when co-transferred with encephalitogenic cells or when injected into recipient animals at a different site at the time encephalitogenic cells were transferred. This suppression was mediated by CD8+ T cells, correlated with suppression of DTH responses to MBP, and was associated with decreased inflammation in the spinal cord. Unlike oral tolerization, spleen cells from i.v. tolerized animals did not suppress adoptively transferred EAE when co-transferred with encephalitogenic cells although i.v. tolerized animals were protected from adoptively transferred EAE. MBP peptides were then utilized to further characterize differences between i.v. and oral tolerization in the actively induced disease model. Both orally and intravenously administered MBP suppressed actively induced EAE. However, EAE was only suppressed by prior i.v. tolerization with the encephalitogenic MBP peptide 71-90, but not with the non-encephalitogenic peptide 21-40, whereas prior tolerization with 21-40 did suppress actively induced EAE when administered orally. These results suggest a different mechanism of tolerance is initiated by oral vs. intravenous administered antigen. Specifically, oral tolerization suppresses primarily by the generation of active suppression whereas the dominant mechanism of suppression associated with i.v. tolerization appears most consistent with the elicitation of clonal anergy.

Administration, Oral↗
PubMed2005

Infectious tolerance develops after intrathymic alloantigen-induced acceptance of rat heart allografts can be adoptively transferred.

BACKGROUND: We have shown that intrathymic (IT) injection of alloantigen with antirat lymphocyte serum (ALS) treatment can induce donor-specific allograft acceptance. The purpose of this study was to investigate whether T-regulatory (T-reg) cells play a role in the maintenance of donor-specific heart graft tolerance that develops after IT injection of Lewis (LEW, RT1(l)) alloantigen into a Dark Agouti (DA, RT1(a)). METHODS: Naïve DA rats were injected IT with 2.5 x10(7) LEW donor splenocytes and injected intraperitoneally with 1 mL ALS. Twenty-one days after pretreatment, a LEW or Brown Norway (BN, RT1(n)) heart was transplanted into a treated DA recipient. Splenocytes (1 x 10(8) or 5 x 10(7)) from a LEW heart-tolerant long-term survivor (LTS; >60 days) DA recipient were harvested and adoptively transferred (AT) into an irradiated (450 rad) naïve DA rat 24 hours before transplanting a LEW heart. RESULTS: All LEW heart allografts were rejected by untreated DA rats in a mean survival time (MST) of 7.4 +/- 1.7 days (n=7). In contrast, 66.7% of LEW heart grafts into IT+ALS-pretreated DA recipients were accepted indefinitely (n=24). When either 1 x 10(8) (n=5) or 5 x 10(7) (n=5) splenocytes from a LEW heart graft-tolerant LTS (>60 days) DA recipient were AT into a new naïve DA rat, all new LEW heart grafts were accepted indefinitely. CONCLUSIONS: The donor-specific tolerance that develops after IT+ALS-induced LEW heart acceptance by DA recipients can be transferred adoptively to new naïve DA recipients, thus indicating that it is infectious tolerance.

Adoptive Transfer↗
PubMed1984

Analysis of the involvement of cells from donor and recipient mice in adoptive transfer of antitumor immunity.

In this study, we attempted to analyze the effector cells for adoptive transfer of protective immunity directed against a P815Ys tumor. The spleen, lymph node, and peritoneal exudate cells obtained from immune mice at Day 7 to Day 10 after last challenge were tested for their in vitro cell-mediated cytotoxicity against P815Ys cells, using a 4-hr 51Cr release assay. The immune spleen lymphocytes (ISL) showed no cytotoxicity, whereas the peritoneal exudate cells exhibited marked cytotoxicity. Unexpectedly, when ISL or peritoneal exudate cells were adoptively transferred i.v. into mice bearing the P815Ys tumor, it was the ISL but not the peritoneal exudate cells that provided the hosts with significant protection. Using alloantibodies for negative depletion of cells in ISL, it was found that, after treatments with anti-Thy 1.2 or anti-Lyt 1 antiserum plus complement but not with anti-Lyt 2 or complement alone, the protective capacity of ISL can be abolished, indicating that the effector cells for conferring protective immunity to the host are Lyt 1-bearing T-cells. Moreover, culture supernatants of ISL with or without mitomycin C-treated P815Ys contain helper factor, interferon, and interleukin 2, which enhanced the in vitro generation of cell-mediated cytotoxicity against P815Ys. Taken together, these results strongly suggest that the donor helper T-cells are the effector cells responsible for adoptive transfer of protective immunity. We next examined the contribution of host cells. Syngeneic mice were made to become either T-cell (with thymectomy and irradiation)- or macrophage (with the administration of silica) depleted and were then subjected to adoptive transfer experiments. Both the thymectomized and the silica-treated mice, after receiving the ISL, showed significantly better survival times than did normal mice. Thus, the data suggest that the elimination of T-cells or inactivation of macrophages, presumably with immunosuppressive activity in the recipients, will allow further improvement of their battle for survival against tumor.

Animals↗
PubMed2005

Adoptive transfer of macrophages ameliorates renal fibrosis in mice.

We performed adoptive transfer of bone marrow-derived (BM) macrophages following pharmacological depletion of leukocytes in a mouse model of unilateral ureteral obstruction (UUO). Treatment with cyclophosphamide (CPM) caused marked decrease in the numbers of F4/80-positive interstitial macrophages as well as in peripheral blood leukocyte counts, and adoptive transfer of BM macrophages to CPM-treated mice resulted in significant increase in the numbers of interstitial macrophages both at day 5 and at day 14 after UUO. At day 5 after UUO, no significant change was observed in the degree of renal interstitial fibrosis either by treatment with CPM or with CPM+macrophage. However, at day 14 after UUO, treatment with CPM caused significant increase in the degree of interstitial fibrosis, and adoptive macrophage transfer to these mice attenuated this enhancement in renal fibrosis. Our result suggests the role of infiltrating macrophages on facilitating tissue repair at late stage of UUO.

Adoptive Transfer↗
PubMed1994

Adoptive transfer of experimental allergic encephalomyelitis: recipient response to myelin basic protein-reactive lymphocytes.

We have used adoptive transfer of myelin basic protein (MBP)-reactive lymphocytes in the Lewis rat model of experimental allergic encephalomyelitis (EAE) to identify stages of effector cell development and to investigate the nature of the subsequent recipient response to the transferred cells. Depending on the timing of cell collection, lymph node cells (LNC) obtained from MBP-CFA (MBP emulsified in complete Freund's adjuvant)-immunized donors may directly transfer clinical disease; however, independent of disease development, recipients of LNC develop early onset of clinical disease following immunization of the recipients with MBP-CFA, consistent with the presence of MBP-memory cells in the LNC transfer inoculum. Similarly obtained spleen cells do not directly transfer disease and do not contain MBP-memory cells (as defined by the early onset of clinical disease following MBP-CFA challenge). Spleen cells adoptively transfer clinical disease only following in vitro culture stimulation with antigen or selected mitogens. Recipients of the primary culture-derived encephalitogenic spleen cells also develop an accelerated onset of clinical disease following MBP-CFA challenge, indicative of the presence of MBP-memory cells, and are not vaccinated. Encephalitogenic T cell lines adoptively transfer clinical disease, and in most cases recipients are vaccinated to MBP-CFA-induced active disease, but remain susceptible to adoptively transferred disease. Co-transfer of encephalitogenic T cell line cells with MBP-reactive lymph node or encephalitogenic spleen cells does not alter the vaccination response. We have found that during the process of T cell line development, the vaccinating phenotype is acquired following the second antigen stimulation cycle. These studies also demonstrate that regulation induced by T cell vaccination blocks the development of effector cells from precursor cells and that such regulation is also equally effective in blocking disease development in recipients which have increased numbers of memory cells. Thus, the response to T cell vaccination, once established, is fully capable of inhibiting the development of effector cells from increased numbers of precursor/memory cells, a response that would be needed in the clinical application of vaccination-induced resistance.

Animals↗
PubMed1997

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

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

Adoptive Transfer↗
PubMed1981

In vitro growth of murine T cells. VI. Accelerated skin graft rejection caused by adoptively transferred cells expanded in T cell growth factor.

The ability of adoptively transferred cytotoxic T cells expanded in T cell growth factor (TCGF) to induce accelerated graft rejection of B10.BR skin grafts from normal B6AF1 recipient mice was tested. In vitro sensitized cells expanded in regular TCGF were capable of accelerating graft rejection when adoptively transferred i.v. 1 day after grafting. Cells expanded in LF-TCGF (lectin-free) were more effective in accelerating graft rejection than cells expanded in lectin containing TCGF. Nonsensitized cells or cells sensitized to irrelevant B10.D2 antigenic determinants in vitro and subsequently expanded in LF-TCGF were unable to induce accelerated rejection of the B10.BR grafts. Expanded cytotoxic effector cells known to be immunologically active in vivo were also unable to accelerate graft rejection if irradiated with 2000 R before adoptive transfer. The ability of cells to lyse the appropriate targets in 4-hr 51Cr release assays correlated poorly with the effectiveness of these cells after in vivo injection. These studies are the first to demonstrate that cytotoxic cells expanded in TCGF are capable of mediating a cytotoxic function in vivo.

Animals↗
PubMed1986

Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors.

We describe a quantitative intrathymic (i.t.) adoptive transfer system for detecting thymocyte precursor cells in rats and mice. In this system, the generation of donor-origin thymocytes is analyzed on the FACS after the injection of test cells directly into the thymus of sublethally irradiated, histocompatible, RT-7 (rat) or Ly-1 (mouse) alloantigen-disparate recipients. Like the standard i.v. adoptive transfer assays for prothymocytes, the i.t. transfer assay is time, dose, and irradiation dependent. However, unlike the i.v. assays, the i.t. assay is highly sensitive, independent of cell migration, and specific for T-lineage precursor cells. Thus, the i.t. system requires between 25- and 50-fold fewer precursor cells than do the i.v. systems to generate a given number of donor-origin thymocytes; it detects nonmigratory as well as migratory subsets of precursor cells; it detects prethymic and intrathymic precursor cells with equal facility; and it produces a discrete, self-limited wave of donor-origin thymocytes and peripheral T cells. Moreover, neither hemopoietic nor lymphopoietic stem cell chimerism occurs at extrathymic sites. Comparison of the kinetics of thymocytopoiesis in the i.t. and i.v. transfer systems suggest that the seeding efficiency of prothymocytes in the i.v. assay approximates 0.04; the lag phase of the time-response curve is not due to a delay in the entry of prothymocytes into the thymus; and the relative amount of thymocyte precursor activity in various lymphohemopoietic tissues is highest in bone marrow, lowest (or absent) in lymph node, and intermediate in spleen, blood, and thymus. Moreover, the occurrence of saturation kinetics in the dose-response curve of the i.t. system supports the hypothesis that a finite number of microenvironmental niches for prothymocytes may exist in the thymus. These initial observations will require confirmation and extension in future studies. However, based on the present findings and related observations, we anticipate that the i.t. adoptive transfer system will contribute importantly to the definitive analysis of both normal and abnormal thymocytopoiesis.

Animals↗
PubMed1981

Allotype suppression induced in the adoptive transfer system: the variables of the system and an apparent absence of a role for T cells.

A study has been made of the variables concerned in allotype suppression of adult spleen cells in the adoptive transfer system. These are; SRBC (antigen) dose; the dose and timing of injection of anti-allotype serum IgG; the number of spleen cells transferred and whether these cells were taken from primed or unprimed donors. Adoptively transferred primed cells are considerably less susceptible to suppression by concomitantly injected anti-allotype serum IgG than are unprimed spleen cells. Injection of anti-allotype serum during the period after adoptive transfer, has shown that primed cells loose their susceptibility sooner (2 days) than the unprimed cells (4 days). Allotype heterozygous CBA spleen cells are less susceptible heterozygous CBA spleen cells are less susceptible to allotype suppression than either allotypically homozygous or heterozygous non-H-2k cells (H-2b,d, or s). Allotype suppression of the TI IgG response to DNP-Ficoll was measured 7 days after adoptive transfer of allotype-homozygous cells from both normal and nude CBA mice (unprimed). The results indicate that T cells do not play a role in the initiation of short-term allotype suppression in the adoptive transfer system.

Animals↗
PubMed1993

Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors.

Precise definition of the role of both CD4 and CD8 T-cell subsets from NOD mice in the adoptive transfer of diabetes has been complicated by the possibility that endogenous T-cells may be recruited. Two newly created NOD congenic stocks, NOD.NON-Thy-1a and NOD/LtSz-scid, have been used as T-cell donors and recipients, respectively, to eliminate contributions from endogenous T-cells and thus to define the requirement for transferred T-cell subsets as a function of underlying diabetes development in the NOD donor. Total T-cells and T-cell subsets prepared from either prediabetic or diabetic NOD.NON-Thy-1a donors were adoptively transferred into 6-wk-old NOD-scid/scid recipients that were monitored for diabetes development. Both flow cytometric and histological analysis of recipient spleen and pancreas after adoptive transfer showed lymphocytes of donor (Thy1.1+) origin exclusively. Total T-cell and enriched CD4+ T-cell preparations from both diabetic and young prediabetic donors transferred diabetes to NOD-scid/scid recipients. However, the mean time to diabetes onset was doubled when CD4+ lymphocytes were isolated from prediabetic versus diabetic donors, and these transfers were complicated by the generation of small but significant numbers of CD8+ cells over time. Enriched CD8+ populations alone were unable to transfer disease. More rigorous exclusion of CD8+ cells by means of anti-CD8 MoAb treatment in vivo of the recipients of enriched CD4+ cells demonstrated a significant difference in the diabetogenic potency of CD4+ lymphocytes from diabetic versus nondiabetic donors. Diabetes was adoptively transferred to 58% of the recipients of enriched CD4+ lymphocytes from diabetic donors. In contrast, none of the recipients of enriched CD4+ lymphocytes from young prediabetic donors developed diabetes after MoAb treatment in vivo. The ability of a T-cell population to produce severe insulitis and sialitis in NOD-scid/scid recipients of T-cells closely paralleled its ability to induce diabetes. In an effort to suppress insulitis by suppression of macrophage migration to the islets, NOD-scid/scid mice were treated with silica in conjunction with adoptive transfer of T-cells from diabetic donors. Chronic silica treatment failed to deplete tissue macrophages and did not prevent diabetes development after transfer of unfractionated T-cells. Evidence is discussed indicating that the age-associated differences in ability of CD4+ T-cells to adoptively transfer diabetes in the absence of the CD8+ T-cells subset is a function of prior, chronic exposure of the CD4+ lymphocytes to beta-cell antigens in the donor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Cell migration studies in the adoptive transfer of adjuvant arthritis in the Lewis rat.

Adjuvant arthritis (AA) can be induced in Lewis rats by a single injection of either heat-killed Mycobacterium tuberculosis or the lipoidal amine CP20961. Concanavalin A (Con A)-stimulated T cells isolated from AA rats are able to adoptively transfer the disease to naive syngeneic recipients. It is unclear, however, whether these transferred cells traffic directly to the joint and initiate arthritis, or whether secondary host cells are responsible for activation of the disease. In the current investigation, T cells labelled with the vital fluorescent dyes Hoechst H33342 and Zynaxis PKH26-G were used to adoptively transfer adjuvant disease to naive recipients. At various stages of disease development sections of ankle joints, together with a range of soft tissues, were examined by fluorescence microscopy to determine the distribution of labelled donor cells in the recipients. Intensely fluorescent lymphocytes were observed in the liver, spleen and lymph nodes within 24 hr of adoptive transfer. Foci of such cells were clearly visible in the primary lymphoid tissues as late as 14 days after transfer. However, close examination of both ankle joint sections and patellar fat pad cells throughout the time-course of the study failed to detect any labelled cells at the lesion site. To develop these observations further, we performed adoptive transfers to nude Lewis rats (rnu/rnu) and found that they were only moderately sensitive and developed, at best, a transient arthritis. This observed difference could not be explained by a generalized lack of an inflammatory response, since we were able to elicit a zymosan peritonitis in the nude rats. However, in nude Lewis rats a striking increase in adoptively transferred AA was obtained after reconstitution with 4 x 10(8) naive syngeneic spleen cells. These combined observations suggest that a host-derived immune cell population is crucial for arthritis induction in the adoptive transfer system.

Animals↗
PubMed1997

Adoptive transfer of murine cytomegalovirus-immune lymph node cells prevents retinitis in T-cell-depleted mice.

PURPOSE: The purpose of this study was to determine whether adoptive transfer of murine cytomegalovirus (MCMV)-immune lymph node cells prevents retinitis in immunosuppressed mice. METHODS: Adult BALB/c mice were thymectomized and T-cell depleted using rat monoclonal antibodies specific for mouse CD4+ and CD8+ T-cells. The level of rat immunoglobulin G in the treated mice was monitored by enzyme-linked immunosorbent assay. Immune cells were labeled with PKH26-GH immediately before adoptive transfer, and flow cytometry was used to determine the percentage of adoptively transferred T-cells (PKH+, fluorescein isothiocyanate [FITC+]) in the spleens of the recipient mice 3 days after transfer. The ability of adoptively transferred cells to protect from retinitis was studied in T-cell-depleted mice injected with MCMV through the supraciliary route. Mice received 4 x 10(7) in vitro-restimulated MCMV-immune cells, 4 x 10(7) freshly isolated MCMV-immune cells, 4 x 10(7) freshly isolated ovalbumin-immune cells, or no cells (control group). RESULTS: The best time to balance depletion of endogenous T-cells with persistence of transferred cells was 3 weeks after T-cell depletion. Both restimulated and freshly isolated MCMV-immune cells conferred protection from retinitis. Freshly isolated ovalbumin-immune lymph node cells did not prevent retinitis, indicating that protection was virus-specific and merely was not because of transfer of antigen-activated lymph node cells. CONCLUSIONS: Adoptive immunotherapy has been used to prevent cytomegalovirus (CMV) infection in patients who have undergone transplantation, and, by extrapolation, the results of these studies suggest that adoptive immunotherapy with human CMV-specific immune cells might be used to prevent or ameliorate CMV retinitis in immunocompromised patients.

Animals↗