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Biomedical subjects

K Nomoto

Publications and source records attributed to K Nomoto.

At least 55 records · Page 3Linked to original sources
PubMed2001

Antitumor effects of the intravesical instillation of heat killed cells of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2.

PURPOSE: To characterize the potential of heat killed Lactobacillus casei, Shirota strain (LC9018), as an alternative to bacillus Calmette-Guerin (BCG) for treating patients with bladder cancer we investigated the antitumor effects of intravesical instillation of LC9018 in the MBT-2 orthotopic bladder tumor implantation model in C3H/He mice. MATERIALS AND METHODS: LC9018 or BCG, Tokyo 172 strain, was instilled once daily for 10 days starting on the day after orthotopic implantation of MBT-2. Tumor appearance and mean bladder weight on day 21 after tumor implantation were evaluated. Moreover, we investigated the augmentation of local cellular immunity in bladder mucosa by immunohistochemical staining and reverse transcription polymerase chain reaction. RESULTS: Intravesical LC9018 instillation significantly reduced the rate of tumor appearance in 8 of 38 subjects (p <0.001) and mean tumor growth plus or minus standard deviation with a bladder weight of 37 +/- 49 mg. (p <0.001) compared with tumor appearance in 41 of 58 subjects and mean bladder weight 146 +/- 183 mg. in controls. BCG had no significant antitumor activity in the orthotopic implantation model. Intravesical instillation of LC9018 augmented the local expression of antitumor cytokine messenger RNA (interferon-gamma and tumor necrosis factor-alpha) and induced the infiltration of neutrophils surrounded by macrophages that phagocytosed LC9018 cells at the bladder mucosa. CONCLUSIONS: These results suggest that LC9018 is potentially more potent and safer as a therapeutic agent than BCG for superficial bladder tumors. Furthermore, the antitumor effect of LC9018 is exerted via the augmentation of local cell mediated antitumor immunity.

Administration, Intravesical↗
PubMed2000

The impact of donor age on living donor liver transplantation.

BACKGROUND: The impact of the age of the donor on the outcome of living related liver transplantation is yet to be clarified. METHODS: During October 14, 1996 and December 20, 1999, 34 living related liver transplantations were performed. Of these, 26 cases were performed using the extended left lobe graft, which were classified into three groups; younger donor group (group Y, donor age < 30, n = 7), middle-aged donor group (group M, 30 < or = donor age <50, n=13), and older donor group (group O, donor age < 50, n = 6). Early allograft function and regeneration were compared between these groups. RESULTS: There was no difference in standard liver volume, and predicted or harvested graft size between the three groups. Although serum transaminase and total bilirubin levels within postoperative day 7 were not different between the groups, the prothrombin time on postoperative day 3 was significantly longer in group O than in group Y. One week after transplantation, group Y had significantly greater graft/standard liver volume ratio than group O, and greater graft volume than group M and O. One month after transplantation, however, there was no significant difference in such graft size parameters between the groups. Graft and patient survival were comparable between the three groups. CONCLUSION: Although function and regeneration of the allografts from older donors in living donor liver transplantation is worse than those of their younger counterparts, the outcome is not affected by the age of the liver.

Adult↗
PubMed2000

Breakdown of Th cell immune responses and steroidogenic CYP11A1 expression in CD4+ T cells in a murine model implanted with B16 melanoma.

The association between the balance of Th1/Th2 cell responses and CYP11A1 expression in CD4+ T cells was investigated in a murine model implanted with highly metastatic B16F10 melanoma cells (B16F10 mice). When 2 x 10(5) cells/mouse of B16F10 cells were inoculated into C57BL/6 mice, Th2 cell responses and pulmonary metastasis were increased. In addition, corticosterone levels in splenic tissue or serum and CYP11A1 mRNA expression (mRNA encoding cholesterol side-chain cleavage p450 enzyme) in CD4+ T cells were increased in these mice. When the anti-corticosterone drug aminoglutethimide (CYP11A1 inhibitor) was administered to B16F10 mice, corticosterone levels in splenic tissue or serum and CYP11A1 mRNA expression were decreased at 14 days after tumor inoculation. In addition, Th1 cell responses were restored and pulmonary metastasis was reduced by aminoglutethimide. These results indicated that the breakdown of Th cell responses and increase of pulmonary metastasis were due to an increase in steroidogenic CYP11A1 mRNA expression in CD4+ T cells. Moreover, it was suggested that promotion of CYP11A1 mRNA expression in Th2 cells was partially involved due to an increase in level of corticosterone in splenic tissue and the breakdown of Th cell responses locally in the splenic tissue, which then affected the maintenance of Th2 cell functions in the microenvironment of tumor-bearing mice.

Aminoglutethimide↗
PubMed2000

Domino liver transplantation from a living related donor.

BACKGROUND: Although domino liver transplantations (OLT) from cadaveric donors have been performed in about 50 cases since 1995, only one case in the Japanese literature has been reported on a domino OLT from a living related donor. The difficulties of the later surgery lie in the small size of the graft volume and the short length of the vascular cuffs in the graft. METHODS: The left lobe graft was procured from a 43-year-old younger brother of a familial amyloidotic polyneuropathy (FAP) patient. Next, the left lobe graft (510 g, 44% of the estimated standard liver volume of the FAP patient) was implanted into the 48-year-old female FAP patient. At surgery for the FAP patient, a sufficient length of the vascular cuffs was secured by an extended left lobe resection, although the right lobe graft was able to maintain sufficient vascular cuffs. The right lobe graft (720 g, 54% of the recipient's estimated standard liver volume) was then implanted in the 43-year-old male patient with liver cirrhosis and hepatocellular carcinoma (stage IV-A). RESULTS: The two recipients were discharged from the hospital 1 month after OLT. At 7 months after OLT, they are both doing well and the domino recipient is free of any tumor recurrence. CONCLUSION: A domino OLT from the living related donor can therefore be done safely when careful attention is paid to the graft volume and the length of the vascular cuffs for anastomosis.

Amyloid Neuropathies↗
PubMed2000

Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice.

One of the most intriguing features of gammadelta T cells that reside in murine epithelia is the association of a specific Vgamma/Vdelta usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the "first wave" Vgamma5+ fetal thymocytes and overwhelmingly express the canonical Vgamma5/Vdelta1-TCRs lacking junctional diversity. Targeted disruption of the Vdelta1 gene resulted in a markedly impaired development of Vgamma5+ fetal thymocytes as precursors of DETCs; however, gammadeltaTCR+ DETCs with a typical dendritic morphology were observed in Vdelta1-/- mice and their cell densities in the epidermis were slightly lower than those in Vdelta1+/- epidermis. Moreover, the Vdelta1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes. Vgamma5+ DETCs were predominant in the Vdelta1-/- epidermis, though Vgamma5- gammadeltaTCR+ DETCs were also detected. The Vgamma5+ DETCs showed a typical dendritic shape, gammadeltaTCR(high), and age-associated expansion in epidermis as observed in conventional DETCs of normal mice, whereas the Vgamma5- gammadeltaTCR+ DETCs showed a less dendritic shape, gammadeltaTCR(low), and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular Vgamma/Vdelta-chain usage but requires expression of a limited diversity of gammadeltaTCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.

Animals↗
PubMed2000

Mixed chimerism, heart, and skin allograft tolerance in cyclophosphamide-induced tolerance.

We elucidated the possible role of chimerism in skin and heart allograft tolerance using cyclophosphamide (CP)-induced tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were i.v. primed with 1x10(8) spleen cells (SC) from H-2 matched AKR (H-2k; Thy1.1, Mls-1a) mice and then treated i.p. with 200 mg/kg of CP, the survivals of both AKR skin grafts and heart grafts (HG) were permanently prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree of mixed chimerism, the clonal destruction of Mls-1a-reactive CD4+Vbeta6+ T cells in the periphery, and the clonal deletion of Vbeta6+ thymocytes were all observed. When AKR SC and 100 mg/kg CP were used for conditioning, the AKR HG were permanently accepted, but the survival of the AKR skin grafts was only mildly prolonged. The clonal destruction of CD4+Vbeta6+ T cells in the periphery and the intrathymic clonal deletion of Vbeta6+ thymocytes were induced in both the SC and the 100 mg/kg CP-treated C3H mice. A minimal degree of mixed chimerism was detectable at 4 and 12 weeks after AKR SC and 100 mg/kg CP treatment, and still did not disappear at 40 weeks. The degree of mixed chimerism induced with SC and 100 mg/kg CP was significantly lower than that with SC and 200 mg/kg CP during the observation. No posttransplant cardiac allograft vasculopathy (CAV) was observed to develop, while both the Th1 type (interferon-gamma) and Th2 type (interleukin-4 and -10) cytokine expressions decreased in the AKR HG of the tolerant C3H mice treated with both AKR SC plus 200 mg/kg CP, and AKR SC plus 100 mg/kg CP. A second set of skin grafts from donor AKR mice survived for more than 100 days in a tolerogen-specific fashion in all C3H mice treated with AKR SC and 200 mg/kg CP and also accepted the AKR HG for over 200 days, while 80% of the C3H mice treated with AKR SC and 100 mg/kg CP and accepted the AKR HG for more than 200 days. These results strongly suggested the following conclusions: 1) the degree of chimerism can strongly influence the induction of skin and heart allograft tolerance, 2) posttransplant CAV does not develop in the donor HG maintained by chimerism-based CP-induced tolerance, 3) the mRNA expression of both Th1 and Th2 type cytokine decreased in the donor HG maintained by chimerism-based CP-induced tolerance, and 4) the induction of skin allograft tolerance is more difficult than the prevention of posttransplant CAV.

Animals↗
PubMed2000

Induction of permanent mixed chimerism and skin allograft tolerance across fully MHC-mismatched barriers by the additional myelosuppressive treatments in mice primed with allogeneic spleen cells followed by cyclophosphamide.

A pure method of drug (cyclophosphamide plus busulfan)-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers in mice has been established. The components of the method are i.v. administration of 1 x 108 allogeneic spleen cells on day 0, i.p. injection of 200 mg/kg CP and 25 mg/kg busulfan on day 2, and i.v. injection of T cell-depleted 1 x 107 bone marrow cells from the same donor on day 3. Recipient B10 (H-2b; IE-) mice prepared with this conditioning developed donor-specific tolerance, and long-lasting survival of skin allografts was shown in almost of the recipient mice. In the tolerant B10 mice prepared with new conditioning, stable multilineage mixed chimerism was observed permanently, and IE-reactive Vbeta11+ T cells were reduced in periphery as seen in untreated B10.D2 (H-2d; IE+) mice. The specific tolerant state was confirmed by the specific abrogation against donor Ag in the assays of CTL activity and MLR and donor-specific acceptance in the second skin grafting. These results demonstrated that the limitation of standard protocol of cyclophosphamide-induced tolerance, which have been reported by us since 1984, can be overcome by the additional treatments with the myelosuppressive drug busulfan, followed by 1 x 107 T cell-depleted bone marrow cells. To our knowledge, this is the first report to induce allograft tolerance with a short course of the Ag plus immunosuppressive drug treatment without any kind of mAbs (pure drug-induced tolerance).

Animals↗
PubMed2000

Impacts of the Detection of Cassiopeia A Point Source.

Very recently the Chandra first light observation discovered a point-like source in the Cassiopeia A supernova remnant. This detection was subsequently confirmed by the analyses of the archival data from both ROSAT and Einstein observations. Here we compare the results from these observations with the scenarios involving both black holes (BHs) and neutron stars (NSs). If this point source is a BH, we offer as a promising model a disk-corona type model with a low accretion rate in which a soft photon source at approximately 0.1 keV is Comptonized by higher energy electrons in the corona. If it is an NS, the dominant radiation observed by Chandra most likely originates from smaller, hotter regions of the stellar surface, but we argue that it is still worthwhile to compare the cooler component from the rest of the surface with cooling theories. We emphasize that the detection of this point source itself should potentially provide enormous impacts on the theories of supernova explosion, progenitor scenario, compact remnant formation, accretion to compact objects, and NS thermal evolution.

Journal Article↗
PubMed2000

A Model for the Quiescent Phase of the Recurrent Nova U Scorpii.

A theoretical light curve is constructed for the quiescent phase of the recurrent nova U Scorpii in order to resolve the existing distance discrepancy between the outbursts (d approximately 6 kpc) and the quiescences (d approximately 14 kpc). Our U Sco model consists of a very massive white dwarf (WD), an accretion disk (ACDK) with a flaring-up rim, and a lobe-filling, slightly evolved, main-sequence star (MS). The model properly includes an accretion luminosity of the WD, a viscous luminosity of the ACDK, and a reflection effect of the MS and the ACDK irradiated by the WD photosphere. The B light curve is well reproduced by a model of 1.37 M middle dot in circle WD + 1.5 M middle dot in circle MS (0.8-2.0 M middle dot in circle MS is acceptable) with an ACDK having a flaring-up rim and the inclination angle of the orbit i approximately 80&j0;. The calculated color is rather blue (B-V approximately 0.0) for a suggested mass accretion rate of 2.5x10-7 M middle dot in circle yr-1, thus indicating a large color excess of E(B-V) approximately 0.56 with the observational color of B-V=0.56 in quiescence. Such a large color excess corresponds to an absorption of AV approximately 1.8 and AB approximately 2.3, which reduces the distance to 6-8 kpc. This is in good agreement with the distance estimation of 4-6 kpc for the latest outburst. Such a large intrinsic absorption is very consistent with the recently detected period change of U Sco, which is indicating a mass outflow of approximately 3x10-7 M middle dot in circle yr-1 through the outer Lagrangian points in quiescence.

Journal Article↗
PubMed2000

The Properties of Supernova 1997cy Associated with GRB 970514.

The extraordinary SN 1997cy associated with GRB 970514 has been observed photometrically and spectroscopically for nearly 2 yr. At the time of discovery, SN 1997cy was the brightest supernova (SN) ever observed (MV</=-20.1, vhel=19,140 km s-1, H0=65 km s-1 Mpc-1). Up to the last available observations (600 days after the gamma-ray burst), the total time-integrated flux was equal to or larger than that expected from the complete thermalization of the gamma-rays produced by 2.3 M middle dot in circle of 56Co. However, starting already on day 60 the luminosity decline is slower than the 56Co decay rate, indicating that the SN ejecta was interacting with circumstellar material (CSM). The interaction appeared to weaken around day 550. The spectra of SN 1997cy are dominated at all epochs by Halpha emission, which shows at least three components of different widths, as in SN 1988Z. Several other lines with different widths are also visible, especially at early epochs. The entire light curve of SN 1997cy is reproduced by a model of the interaction of the very energetic (E=3x1052 ergs) ejecta of a massive star (25 M middle dot in circle) with the CSM, with some contribution from radioactive decays. The CSM could have been ejected with a mass-loss rate of M&d2; approximately 4x10-4 M middle dot in circle yr-1 as the progenitor star evolved from a blue to a red supergiant about 104 yr before the explosion. The lack of oxygen and magnesium lines in the spectra at nebular phases poses a problem for models requiring high-mass progenitors. The possibility that most of the core material of the progenitor has fallen onto a massive black hole so that the reverse shock dies at the inner edge of the H/He envelope is discussed.

Journal Article↗
PubMed2000

Accumulation of common T cell clonotypes in the salivary glands of patients with human T lymphotropic virus type I-associated and idiopathic Sjögren's syndrome.

To clarify the pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated Sjögren's syndrome (SS), the TCR Vbeta gene usage by the infiltrating lymphocytes in the target organ was examined. The Vbeta families predominantly used in the labial salivary gland (LSG) from the HTLV-I-seropositive (HTLV-I+) SS patients were more restricted than those from the HTLV-I-seronegative (idiopathic) SS patients, and were commonly Vbeta5.2, Vbeta6, and Vbeta7. The single-strand conformation polymorphism analysis revealed that T cell clonotypes with Vbeta5.2, Vbeta6, and Vbeta7 accumulate in the LSG from the HTLV-I+ and idiopathic SS patients. Among junctional sequences of the most dominant Vbeta7 transcripts, the conserved amino acid motif (QDXG: X is any amino acid) was found in six of the five HTLV-I+ SS patients and was also detected in two of the five idiopathic SS patients. Using the probes specific to the motif, the Vbeta7 transcripts with the motif were detected in the LSG from all of the seven HTLV-I+ and five of the six idiopathic SS patients, but not from eight healthy subjects. The Vbeta7 transcripts with this motif were also detected in the HTLV-I-infected T cell lines obtained from the LSG of an HTLV-I+ SS patient. The accumulation of HTLV-I-infected T cells expressing TCR with the conserved motif was thus indicated. These T cells were commonly present in patients with idiopathic SS and are strongly suggested to most likely be involved in the pathogenesis of both HTLV-I-associated and idiopathic SS.

Adolescent↗
PubMed2000

TCR-independent activation of extrathymically developed, self antigen-specific T cells by IL-2/IL-15.

Naive intrathymically developed T cells, which express foreign Ag-specific TCR, do not express IL-2R. After antigenic stimulation, they express high affinity IL-2R, which enables IL-2 to be used as an autocrine growth factor. On the contrary, extrathymically developed T cells, which express self Ag-specific TCR but are unresponsive to antigenic stimulation, spontaneously express low affinity IL-2R. In this study, we compared the responses of these two subsets of T cells to IL-2R stimulation and examined the influences of TCR-mediated signaling on the responses. IL-2 or IL-15 augmented the proliferative response of Ag-stimulated, intrathymically developed T cells. On the other hand, extrathymically developed T cells proliferated in response to IL-2 or IL-15, independently of Ag stimulation. Furthermore, both IL-2 and IL-15 induced IFN-gamma production of these T cells, which is strikingly augmented by the presence of IL-12. These results revealed functional differences between intrathymically developed, foreign Ag-specific T cells and extrathymically developed, self Ag-specific T cells. The latter can be activated by some inflammatory cytokines, in an Ag-independent manner, similar to NK cells.

Animals↗
PubMed2000

Regulation of vascular smooth muscle cell proliferation by nuclear factor-kappaB and its inhibitor, I-kappaB.

Proliferation of vascular smooth muscle cells (SMC) is a crucial event in the formation of atherosclerotic tissues and is regulated by nuclear transcriptional factors including nuclear factor-kappaB (NF-kappaB). We constructed a reporter gene assay to measure NF-kappaB-dependent transcriptional activity in SMC. Thrombin receptor-activating peptide (TRAP) and basic fibroblast growth factor (bFGF) stimulated SMC proliferation and rapidly enhanced the NF-kappaB transcriptional activity in a dose-dependent manner. 4-Cyano-5,5-bis-(methoxyphenyl)4-pentenoic acid (E5510) significantly inhibited SMC proliferation and also suppressed NF-kappaB transcription stimulated by TRAP and bFGF. In contrast, although tumor necrosis factor (TNF)-alpha activated NF-kappaB transcription, E5510 had no effect on TNF-alpha-induced activation. NF-kappaB was activated after the stimulation of TRAP, bFGF, and TNF-alpha in electrophoretic mobility shift assay, and E5510 suppressed the NF-kappaB activation induced by TRAP and bFGF but not the activation by TNF-alpha. Western blot analysis of I-kappaBalpha and I-kappaBbeta, inhibitors of NF-kappaB, indicated that I-kappaBalpha degradation, rather than I-kappaBbeta degradation, was important in NF-kappaB activation after the stimulation of TRAP and bFGF. PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) kinase, suppressed NF-kappaB transcriptional activity and SMC proliferation. The phosphorylation of ERK1/2 was rapidly induced by TRAP and bFGF but not by TNF-alpha. These results indicate that TRAP and bFGF induced I-kappaB degradation and NF-kappaB activation through a distinct pathway from TNF-alpha and that ERK1/2 may play an important role in NF-kappaB activation induced by TRAP and bFGF.

Animals↗
PubMed2000

Increased urinary nitrate excretion associated with hepatic allograft rejection in experimental rat models and clinical cases.

In this study, we investigated the relationship between excretion of urinary nitrate as a stable end-product of nitric oxide (NO) metabolism and hepatic allograft rejection. In experimental rat models, hepatic allograft rejection was associated with increased nitrate excretion with a peak on postoperative day 5. The severity of the hepatic allograft rejection was dependent on the increased urinary nitrate excretion. No significant increase in urinary nitrate excretion was observed in cases in which effective immunosuppression was achieved. Inducible nitric oxide synthase mRNA expression was upregulated parallel to interferon-gamma gene expression in the graft-infiltrating mononuclear cells and spleen cells from the recipients. In clinical cases, urinary nitrate excretion increased parallel to increased serum cytosolic enzymes that accompanied rejection. These results suggest that urinary nitrate excretion is a useful indicator for the surveillance of graft rejection and the monitoring of therapeutic effects of antirejection treatments.

Animals↗
PubMed2000

Local injections of OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of Th1-type cytokines and CXC3 chemokines.

The effect of local injections with streptococcal preparation OK432 on the antitumor effect induced by adoptive immunotherapy (AIT) was investigated. Draining lymph node cells on day 14 after B7-P815 inoculation were used for AIT after in vitro stimulation. AIT on days 7 and 10 showed no effect on the growth of s.c. established P815 mastocytoma, but local injections with OK432 into the tumor sites on days 3, 6 and 9 resulted in a moderate antitumor effect. On the other hand, the combination therapy significantly suppressed tumor growth, and the tumor-bearing mice survived longer than those receiving only one of the treatment modalities. The significant infiltration of CD4+ or CD8+ T cells and multiple necrosis in the tumor sites were observed only when the tumor-bearing mice were treated with the combination therapy. In addition, a transfer experiment using labeled effector cells revealed these infiltrated CD8+ T cells and CD4 T cells to be derived from the donor and the host respectively. More importantly, the combination therapy clearly led to higher expression of the mRNA for Th1-type cytokines and CXC3 chemokines in the tumor sites than resulted from each of the treatment modalities alone. Collectively, these results indicate that local injections with OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of the Th1-type cytokines and CXC3 chemokines.

Animals↗
PubMed2000

The crucial role of granulocytes in the early host defense against Strongyloides ratti infection in mice.

The involvement of granulocytes in the host early defense against the nematode, Strongyloides ratti, was studied. It was confirmed that granulocytes were effectively depleted for 4 days by anti-granulocyte monoclonal antibody (anti-Gr-1). To examine the involvement of granulocytes in the host defense against migrating larvae, 2,000 S. ratti infective larvae (L3) were inoculated subcutaneously 1 day after antibody treatment. The number of S. ratti eggs secreted in feces (EPG) was higher in the granulocyte-depleted group than in the control group. The number of migrating larvae also increased in the granulocyte-depleted group in accordance with the increase in EPG. Therefore granulocytes are crucial for the host early defense against migrating larvae of S. ratti. Next, the involvement of granulocytes in the intestinal early defense was examined. Mice were treated with the antibody on day 3 post-infection. On that day, almost all inoculated larvae reached the intestine and molted to become adults. EPG on day 5 post-infection was increased by the antibody treatment, but no effect was observed on intestinal worm numbers. The fecundity (EPG/worm number) of S. ratti adult worms in the granulocyte-depleted group was higher than that in the control group. Thus granulocytes are also involved in the intestinal early defense through suppressing fecundity of the adult worms. On the other hand, the depletion of granulocytes had no effect on the late adaptive response against S. ratti adult worms (e.g. number of intestinal mucosal mast cells, time of worm expulsion). These results suggest that granulocytes are mainly involved in the host early defense against parasites.

Animals↗
PubMed2000

Human skin xenograft rejection in CD45 exon-6 knockout mice: the implication of involvement of a direct pathway.

The results of previous studies indicate that only CD4+ T cells generated via the indirect pathway play an essential role in causing discordant skin xenograft rejection. The present study was conducted in an attempt to clarify further the roles of effector T cells generated via direct pathways on discordant xenograft rejection using CD45 exon-6 knockout (CD45-/-; C57BL/6 (B6): H-2b) mice. It has been strongly suggested that CD45 exon-6 knockout mice have profound impairment in T-cell functions via an indirect pathway. When human skin was grafted onto untreated normal C57BL/6 (B6; H-2b) mice, rejection occurred within 12 days; however, in the CD45 exon-6 knockout mice, the grafts lasted for slightly longer as in fully allogeneic C3H (H-2k) skin rejection, with a mean survival time +/- SD of 19.4 +/- 1.5 days and median survival times of 19 days. The difference in survival periods between the human and C3H skin grafts in the CD45 knockout mice was not statistically significant. Both CD4+ and CD8+ T cells seemed activated in the spleens of these CD45 exon-6 knockout mice 10 days after the human skin grafting. These results suggest that effector T cells generated via a direct pathway can cause discordant skin xenograft rejection, and that CD45 exon-6 knockout mice can generate effector T cells via a direct pathway to reject discordant skin xenografts, similarly to fully allogeneic skin allografts.

Animals↗