Helminth ectoparasites of sillaginid fishes (Perciformes: Percoidei) have low species richness

Repeated exposure of Brown Norway (BN) rats to relatively low doses of HgCl2 induces autoantibodies to renal antigens (e.g., laminin) and a membranous glomerulonephropathy characterized by proteinuria. In contrast, Lewis (LEW) rats are "resistant" to the autoimmune effects of mercury and, when exposed to this metal, are protected against experimental autoimmune encephalomyelitis (EAE) and Heymann's nephritis. To date, there is no information on "suppressive" effects of mercury in naturally occurring (so-called "spontaneous") rat models of autoimmune disease. Therefore, we have administered HgCl2 to diabetes-prone (DP) BB rats, animals that spontaneously develop both insulin-dependent diabetes mellitus (IDDM) and thyroiditis. We found that DP rats treated with mercury or water for a period of 40-125 days developed autoantibodies to thyroglobulin, with a higher incidence in HgCl2-injected animals (92% vs. 56% in H2O-injected controls). A novel finding of our study was the detection of autoantibodies to laminin in the same rats, again with an increased incidence after HgCl2 treatment (83% vs. 44%). IgG2a was the most frequently detected isotype of antibodies to laminin, followed by IgG1, IgG2b and IgG2c. The IgG isotype profile suggests that treatment with HgCl2 may activate both Th1 and Th2 lymphocytes in BB rats. In spite of these stimulatory effects on autoantibody responses, we found that there was no difference in the incidence of IDDM and thyroiditis between HgCl2-treated and control animals. We conclude that the suppressive effects of mercury previously observed in EAE and Heymann's nephritis of LEW rats do not occur in "spontaneous" autoimmune IDDM and thyroiditis of BB rats. Therefore, immune suppression caused by HgCl2 cannot be considered a common phenomenon, but may be a genetically determined characteristic of LEW rats, possibly related to a specific or unique cytokine profile of this particular rat strain. In contrast, while mercury does not seem to recruit, induce or rescue regulatory T cell function in DP rats, it does stimulate autoantibody responses in these animals.     

Thiol levels in CD134-defined subsets of rat T lymphocytes: possible implications for HgCl2-induced immune dysregulation

CD134 (OX40), a member of the tumour necrosis factor receptor family, is expressed on activated T cells and mediates T and B cell costimulation. Its expression is increased after exposure to the thiol-binding compound HgCl2 in BN rats, but not in Lewis rats, in association with induction of a T cell-dependent systemic autoimmune syndrome only in BN rats. Intracellular thiols are involved in regulation of activation and death in T lymphocytes. Therefore, we examined intracellular thiol levels in CD134-defined T cell subsets from BN and Lewis rats. Levels of total thiols and glutathione (GSH) were significantly higher in CD134+CD4+ cells than in CD134+CD4+ cells in both strains. In Lewis rats, total thiol levels in CD4+CD134+ cells, but not in CD4+CD134+ cells, were higher than in BN rats. In contrast, BN rats showed higher GSH levels in CD4+CD134+ cells, but not in CD4+CD134+ cells. In vitro exposure to HgCl2 decreased intracellular thiol levels, predominantly in CD4+CD134+ cells. Furthermore, HgCl2-induced enrichment of CD134+ viable cells was inversely correlated to HgCl2-induced cell death. Strain-dependent differences in thiol levels in CD134-defined subsets of CD4+ lymphocytes and subset-specific modification of thiol levels may contribute to differential lymphocyte activation by oxidizing chemicals.     

Susceptibility to mercuric chloride-induced glomerulonephritis is age-dependent: study of the role of IFN-gamma

The repeated administration of low-dose HgCl2 to brown Norway (BN) rats induces an autoimmune syndrome which is characterized by polyclonal B cell activation, high-level synthesis of IgE and IgG1, and massive proteinuria. Data have been presented suggesting that during disease development there is a preferential expansion of CD4+ T cells belonging to the TH2 subset. In the present study it was found that aged BN rats are far less susceptible to the immunopathological effects of HgCl2 compared to their younger counterparts. Whereas rats at 10 weeks of age develop high-level proteinuria upon three repeated injections with HgCl2, animals at 18 to 24 months of age do not release urinary protein under these conditions and develop low-level proteinuria with a delayed onset after five repeated injections with HgCl2. FACScan analysis of splenocytes from old and young rats revealed a defined increase in the frequency of CD45RB(RC)+/CD4+ T cells in the splenocyte population of older rats, suggesting an age-related shift to a more TH1-like phenotype. Moreover, splenocytes of aged rats generated a threefold higher number of IFN-gamma-producing cells than those of young rats upon polyclonal activation in vitro. The administration of neutralizing anti-rat IFN-gamma mono- and/or polyclonal antibodies to aged BN rats just prior to HgCl2 exposure significantly augmented IgE and IgG1 serum levels and exerted a small but significant stimulatory effect on proteinuria in the initial stage but not in the more advanced stages of the renal disease. When antibodies were given 7 days after the beginning of HgCl2 exposure no stimulatory effect on both IgE/IgG1 levels and proteinuria was observed. The data indicate that splenic T cells of aged BN rats possess a higher capacity to release IFN-gamma than those of young rats and that this cytokine functions to downregulate IgG1 and IgE synthesis in HgCl2-exposed BN rats. The findings further suggest that IFN-gamma plays a regulatory role in the development of glomerulonephritis.     

DNA polymorphisms in the chicken growth hormone gene: response to selection for disease resistance and association with egg production

Our previous study demonstrated that Lewis (LEW) rat recipients engrafted with Brown-Norway (BN) rat liver displayed a long-term graft survival and that phenotypic and functional analyses of graft-infiltrating cells on day 6 postgrafting showed a lower proportion and activity of cytotoxic cells in long-term surviving hosts than LEW recipients engrafted with DA rat liver which showed acute rejection on day 9 postgrafting. In order to assess the immunological mechanisms of unresponsiveness, we analyzed the lymphocyte and serum from LEW recipients engrafted with BN liver. Spleen cells from tolerant LEW recipients on day 6 posttransplantation had no suppressor effect on the one-way mixed lymphocyte culture (MLC) reaction. On the other hand, when serum was added to MLC at a concentration of 6% of the total volume, it suppressed the mixed lymphocyte reaction (MLR) toward donor BN cells by 45.6%, but not toward third-party DA stimulator (-0.4%). Adoptive transfer of the serum from tolerant LEW hosts into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidneys from 7.8 +/- 0.2 to 14.7 +/- 1.6 days (p < 0.01), but not of third party DA kidney graft (mean survival time = 9.5 +/- 1.3 days). The in vitro study demonstrated that the suppressor factor in the serum inhibited the production of IL-2 as well as gamma-IFN in MLR. The suppressor factor was absorbed by LEW cells stimulated with BN cells in vitro, indicating that this factor was directed against recognition sites on responder T lymphocytes. These results showed that an antigen-specific tolerogenic factor which recognized the idiotype of the donor was released into the circulation through the process of BN liver grafting.     

Evidence that recipient CD8+ T cell depletion does not alter development of chronic vascular rejection in a rat heart allograft model

Progressive chronic vascular rejection is a central feature of indefinitely surviving WF.1L LEW/Gut (RT1(1)) heart grafts transplanted to LEW (RT1(1)) recipients in unmodified donor-recipient combinations. At 70 days posttransplantation, large vessels of the grafts are characterized by the presence of vasculitis, vasculitis with associated variable myointimal thickening, and occlusive myointimal thickening with minimal or absent concomitant vasculitis. To assess the potential role of CD8+ T cells as critical effectors of chronic vascular rejection in this model, LEW recipients of WF.1L heart grafts were effectively depleted of CD8+ T cells as a result of prior thymectomy and anti-CD8 (MRC OX8) monoclonal antibody administration prior to transplantation. WF.1L heart grafts transplanted to LEW recipients that had undergone prior sham thymectomy and MRC OX8 administration, or thymectomy and administration of antibody-free culture supernatant, provided appropriate controls. At 70 days posttransplantation, large vessels of WF.1L heart grafts in all 3 transplantation groups showed similar morphologic features, which were comparable to those observed in heart grafts of long-surviving unmodified donor-recipient pairs. This study has shown that profound selective depression of recipient CD8+ T cells does not alter the characteristic features of chronic vascular rejection in this rat cardiac model, and provides evidence that CD8+ T cells play no critical role in the initiation or development of progressive vascular damage in this setting.     

Role of passenger leukocytes in allograft rejection: effect of depletion of donor alveolar macrophages on the local production of TNF-alpha, T helper 1/T helper 2 cytokines, IgG subclasses, and pathology in a rat model of lung transplantation

Acute lung allograft rejection is believed to be initiated by passenger leukocytes, such as alveolar macrophages (AM), in the donor organ, which release TNF-alpha, and present alloantigens to host lymphocytes, to up-regulated Th1 cellular and humoral immunity. However, the role of donor AM in local TNF-alpha synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated. By depleting Brown Norway (BN, RT1n) rat lung allografts of AM before transplantation into Lewis rat (LEW, RT1(1)) recipients, the current study determined the role of donor AM in including the production of TNF-alpha, IFN-gamma (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtypes, and rejection pathology in the allograft. The data show that compared with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-alpha, and IFN-gamma production in allograft bronchoalveolar lavage fluid with variable effects on local IL-4 production. Depletion of AM in the donor lung before transplantation affected the local production of several IgG subclasses. However, pretransplant depletion of donor AM had no effect on the development of the pathology of severe acute rejection. These data show that donor AM have a central role in the local synthesis of TNF-alpha and induce the production of IFN-gamma and IgG subtypes, locally, during acute lung allograft rejection. However, depletion of AM before transplantation does not prevent the development of severe acute rejection in BN rat lungs, transplanted into LEW recipients.     

Functional CD4+ T cell subsets defined by expression of CD45RC and NTA260 antigens and age-associated polarization in murine lupus

Using two mAb, one specific to the alternative exon 6-dependent epitope of CD45 molecules (JH6.2) and one a natural thymocytotoxic autoantibody (NTA) with an unknown reactive epitope (NTA260), we subdivided splenic CD4+ T cells from 2-month-old BALB/c mice into five phenotypically distinct subsets. CD45RC+NTA260- (S I) cells were phenotypically analogous to CD4+ T cells predominating in newborn mice and produced a significant amount of IL-2, but not so IL-4, IL-10 or IFN-gamma when stimulated with immobilized anti-CD3 mAb in vitro. They appeared to consist mainly of naive ThP cells. The CD45RC+NTA260+ (S II) subset also produced IL-2, but not other cytokines; however, the IL-2 levels produced were much higher than seen with the S I subset, thereby suggesting the predominance of further maturated ThP cells. The CD45RC-NTA260+ (S III) subset mainly produced IL-4, IL-10, IFN-gamma and less IL-2, and contained memory cells that helped the secondary antibody response to a recall antigen, and hence contained Th2 and probably a mixture of Th0 and Th1 cells. The CD45RC-NTA260- (S IV) subset was a poor responder to the immobilized anti-CD3 mAb. The CD45RCbrightNTA260dull (S V) subset consisted of a small number of cells that were phenotypically analogous to activated CD4+ T cells. While an age-associated decrease in the proportion of S I and less markedly in S II and in turn increase in S III subsets of CD4+ T cells occurred in normal BALB/c mice, autoimmune disease-prone (NZB x NZW)F1 mice showed a marked age-associated decrease in the proportion of not only S I, II but also III subsets. As aged (NZB x NZW)F1 mice carry CD4+ T helper cells for IgG anti-DNA antibody production, such age-associated polarization to the S IV subset appears to be critical in the pathogenesis of autoimmune disease in these mice.     

Similar pharmacological properties of 8-OH-DPAT and alnespirone (S 20499) at dopamine receptors: comparison with buspirone

OBJECTIVE: We investigated whether the induction of antilymphocyte autoantibodies and immune complexes is associated with the activity of HIV replication. METHODS: Viral HIV-1 RNA was measured in the plasma samples of 84 HIV+ hemophilia patients and correlated with the IgM, IgG, IgM/IgG and IgM/IgG/gp120 load of circulating CD4+ lymphocytes, CD4+ and CD8+ cell counts, plasma neopterin levels and in vitro T-cell responses to mitogens and pooled allogeneic stimulator cells. RESULTS: Compared to patients with no immune complexes, on circulating CD4+ lymphocytes, viral load was increased in patients with IgM, IgM/IgG or IgM/IgG/gp120 complexes. Sequential analysis of HIV+ patients showed that peaks of retroviral activity were associated with the subsequent formation of CD4+ lymphocyte-reactive IgM and IgG autoantibodies and gp120-containing immune complexes. CONCLUSION: The induction of autoantibodies and immune complexes attached to CD4+ lymphocytes is associated with periods of increased viral activity in HIV-infected patients.     

Cytolysin gene expression in the islets of diabetic BioBreeding/Worcester rats

Diabetes prone (DP) BB/Wor rats develop spontaneous autoimmune diabetes mellitus caused by a T cell-dependent process that destroys pancreatic beta cells. Neither the inciting immune system defect nor the mechanism by which beta cells are destroyed is known with certainty. DP rats are severely deficient in certain T cell subsets including CD8+ cytotoxic T cells (Tc) and RT6+ T cells. Diabetes-resistant (DR) BB/Wor rats can be rendered diabetic if depleted of RT6+ T cells. To investigate the mechanisms of beta cell destruction in BB rat diabetes, we determined: 1) the relative abundance of Tc and NK cells in the islets of acutely diabetic DP and RT6-depleted DR rats and 2) expression of mRNA encoding cytolysin, a cytolytic pore-forming protein produced by both Tc and NK cells. We found that in the islets of acutely diabetic DP rats NK cells were about three times more abundant than in diabetic RT6-depleted DR rats. Conversely, in the islets of diabetic DR rats, Tc were three times more abundant than NK cells. In addition, cytolysin gene expression was detected in about 60% of the islets of both DP and DR rats. These data suggest that cytolysin may be a mechanism by which Tc and NK cells damage B cells in vivo.     

Genetic study of gold-salt-induced immune disorders in the rat

BACKGROUND: Rheumatoid arthritis patients treated with gold salts occasionally develop a glomerulonephritis and an increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopropanolsulphonate (ATPS) exhibit an increase in serum IgE concentration, produce antilaminin antibodies (Abs) and develop glomerular linear immunoglobulin (Ig) deposits, occasionally a membranous glomerulopathy and vascular granular Ig deposits. Lewis (LEW) rats are resistant. METHODS: The genetic requirements governing the appearance of these manifestations were studied in congenic rats, and in F1 hybrids injected with ATPS. RESULTS: Non-MHC-linked genes from the BN strain were absolutely required for all the traits to be observed. The RT1n (BN) or RT1(1) (LEW) haplotypes at the MHC were permissive for all the manifestations to appear and two RT1(1) alleles were associated with the highest response. However, granular Ig deposits were only observed in RT1n rats. The high serum IgE concentration and the antilaminin Ab level were associated with the presence of glomerular Ig deposits but were not associated with the presence of vascular Ig deposits. CONCLUSIONS: This study shows that susceptibility to ATPS was mainly dependent upon non-MHC-linked BN genes and that the involvement of MHC-linked genes differed depending upon the character considered. There is an epistatic effect between the various genes.     

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. IV. Alterations in cellular glutathione content

The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg++) was related to intracellular glutathione (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl2 as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl2 for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl2; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl2 is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recent thymic emigrants in the rat express a unique antigenic phenotype and undergo post-thymic maturation in peripheral lymphoid tissues

Studies of the functional properties and developmental potentials of immediate post-thymic cells have been hampered by the lack of reliable markers with which to distinguish recent thymic emigrants (RTE) from the bulk of peripheral T cells. In the present study, the intrathymic FITC-labeling technique was used in concert with three-color flow-cytometric analysis to identify, phenotypically characterize, and study the short term fate of RTE in normal rats. The results indicated that between 3 and 4% of total T cells in lymph node and spleen of 5- to 8-wk-old rats had been released from the thymus within the preceding 24 h. Unlike the bulk of the peripheral T cells, which had a Thy1-, CD45RC+, and/or RT6+ phenotype, these RTE were Thy1+, CD45RC-, and RT6-. Furthermore, two discrete subsets of RTE were defined: a major subset (approximately 95%) of CD4+ or 8+ (single positive), TCR-alpha beta hi T cells that resembled medullary thymocytes; and a minor subset (approximately 5%) of CD4+ and 8+ (double positive), TCR-alpha beta low T cells that resembled cortical thymocytes. The following evidence suggested that most if not all Thy1+ T cells in young adult rats are RTE and their immediate descendants: 1) thymectomy (but not sham thymectomy) selectively depleted Thy1+ T cells from lymph node within 3 to 7 days, even in adrenalectomized rats; 2) most FITC-labeled RTE differentiated into Thy1-, CD45RC+, RT6+ T cells within 7 days of release from the thymus; 3) transitional phenotypes of Thy1+ T cells, including Thy1low, CD45RC+, and RT6+, were observed in normal, as well as in intrathymic, FITC-injected rats; 4) most T cells in neonatal rats were Thy1+ and RT6-, whereas their descendants were Thy1- and RT6+. These experiments demonstrate that most RTE in normal rats are phenotypically (and presumably developmentally) immature at the time of release from the thymus, and progressively acquire the phenotypic attributes of more mature T cells post-thymically. These unique phenotypic attributes should expedite the isolation of RTE and their immediate descendants for definitive studies of their developmental and functional properties.     

Restoration of immune abnormalities in diabetic BB rats after pancreas transplantation. I. Macrochimerism of donor-graft-derived RT6+ T cells responsible for restoration of immune responsiveness and suppression of autoimmune reaction

Diabetes-prone (DP) BB rats (RT1(u), RT6.1) spontaneously develop insulin-dependent diabetes mellitus (IDDM) and the disease manifestation resembles that in human IDDM. DP rats are immunodeficient with severe T lymphocytopenia due to the absence of T cells expressing the RT6 differential alloantigen, which have immunoregulatory functions. MHC- and non-MHC-compatible Wistar Furth (WF; RT1(u), RT6.2) pancreases were transplanted into DP rats. WF pancreas grafts were destroyed by IDDM recurrence (insulitis), but not by rejection, with a mean survival time of 65.3 +/- 21.7 days. To prevent the recurrence of IDDM in the grafts, monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 were administered. WF pancreas grafts were indefinitely accepted (>108.0 +/- 26.8 days) in monoclonal antibody-treated DP recipients. The number of T cells was increased and cellular immune responses restored only in the DP rats that had accepted grafts. The increased number of T cells was due to the peripheral appearance of donor-type RT6.2+ T cells, which represented 34.3 +/- 7.0% of total splenic T cells. The cytotoxicity of splenic T cells to WF islet cells was suppressed in the presence of RT6+ T cells in vitro. These findings demonstrated that stable macrochimerism of donor-derived RT6+ T cells could restore the immune responses and prevent the recurrence of IDDM in the DP recipients.     

Pitx2 participates in the late phase of the pathway controlling left-right asymmetry

BACKGROUND: We have studied the role of the different MHC (RT1) subregions in acute natural killer (NK) cell-mediated bone marrow allograft rejection in lethally irradiated, bone marrow cell (BMC) reconstituted rats. METHODS: We employed a series of MHC congenic and intra-MHC recombinant rat strains so that effects of mismatches in defined RT1 subregions could be studied systematically. BMC allograft survival was measured as 125IUdR uptake in the spleen between day 5 and day 7 after irradiation and BMC reconstitution. RESULTS: We found that in certain RT1 haplotype combinations, nonclassical RT1.C disparities by themselves could determine graft rejection (i.e., in the u/av1 recombinant haplotypes), whereas in another combination (between the av1 and c haplotypes) a mismatch for an isolated classical RT1.A region was decisive for engraftment. Thus, PVG.R1 BMC failed to proliferate in PVG rats, differing in the RT1.A region only, whereas in PVG.1U rats rejection could be determined by isolated differences in the RT1.C region (LEW.1WR1). Also, RT1 homozygous rats (RT1.U) rejected semi-allogeneic F1 hybrid BMC. The acute rejection of BMC was mediated by NK cells, as athymic nude rats, lacking alloreactive T cells but with normal alloreactive NK cells, showed the same patterns of rejection as did normal rats. Nude rats also rejected allogeneic lymphocytes, a previously documented NK-mediated phenomenon, with identical requirements of MHC disparity. CONCLUSIONS: This investigation shows that rat effector NK cells are radioresistant, independent of the thymus, and capable of recognizing and rejecting MHC mismatched transplanted BMC on the basis of mismatches in both classical and nonclassical class I regions in vivo. The studies underline the importance also of NK cells in determining BMC allograft survival.     

Immunotoxic effects of mercuric compounds on human lymphocytes and monocytes. III. Alterations in B-cell function and viability

The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCl2 (0-1000 ng) and MeHgCl2 (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in B-cell proliferation in the presence or absence of monocytes. MeHgCl was approximately 10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize IgM and IgG. Analysis of the expression of activation markers indicated that CD69, an early marker of cell activation, was not effected by mercury. In comparison, B-cell expression of the low affinity IgE receptor and the transferrin receptor were significantly reduced. Of particular interest, cells activated by mitogen for 48 hr became refractory to the immunotoxic effects of mercury. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death.     

Effect of a novel immunosuppressant, FK 506, on autoimmune glomerulonephritis in Brown Norway rats

Mercuric-chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway rats. The effects of a new immunosuppressant FK 506 on this model of glomerulonephritis were studied. Brown Norway rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/ week). Rats developed proteinuria at day 7, which reached a plateau level at day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed a strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Coadministration of FK 506 (1 mg/kg s.c. daily) prevented the appearance of proteinuria at day 14 (621.4 +/- 30.5 vs. 2.2 +/- 2.7 mg/day) and the morphological lesions. These findings suggest that FK 506 could be useful for the therapy of certain types of human glomerulonephritis.