Evidence That Cyclosporine Treatment Causes the Appearance in Rat Lymph Node of T Cells Having the Antigenic Phenotypes of Cortical Thymocytesnode

Chen-Woan, M; Goldschneider, Irving

doi:10.1097/00007890-199103000-00023

Cited by 16 publications

(16 citation statements)

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“…Our results contradict two previous observations: the leakage of cortical thymocytes in the periphery [7,8], and the delayed recovery of CD4 cells in experimental rats suggesting the importance of Th cells [13]. Tri-colour flow cytometry for examination of CD4 and CD8 expression in combination with TCR enabled us to determine CD4 + and CD8 + T cells.…”

Section: Discussioncontrasting

confidence: 79%

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Beijleveld

Groen

Broeren

et al. 1996

Clinical and Experimental Immunology

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SUMMARYLethally irradiated Lewis (LEW) rats reconstituted with syngeneic bone marrow and given CsA for a 4-week period, develop, upon withdrawal of CsA, a graft-versus-host-like disease, so-called CsA-induced autoimmunity (CsA-AI). This T cell-mediated autoimmune disease is thymus-dependent; it is generally held that this disease is a consequence of aberrant T cell recovery brought about by CsA. In this study we determined mononuclear cell subsets phenotypically by tri-colour flow cytometry. A strong decrease in recent thymic emigrants (Thy1.1 + , TCR ® ¯ + ) was observed as a consequence of CsA treatment, eventually resulting in decreased absolute peripheral T cell numbers. In these rats no altered CD4:CD8 T cell ratio was observed before onset of CsA-AI; CD4 + and CD8 + cells consisted predominantly of monocytes (CD4 dim+ , TCR ® ¯ -) and natural killer cells (CD8 + , TCR ® ¯ -), respectively. LEW rats, xirradiated, syngeneic bone marrow-reconstituted and treated with CsA, showed a marked and persistent, relative expansion of mature CD45RC + , RT6 -Th cells. In contrast, Brown-Norway rats treated in a similar fashion, or LEW rats subjected to either CsA treatment or x-irradiation, did not show a comparable expansion of mature CD45RC + , RT6 -Th cells, nor did these animals develop CsA-AI. The CD45RC + , RT6 -Th cells produced IL-2, and moreover constituted the only Th subset producing IFN-°u pon stimulation, and therefore were considered as Th1-like effector cells. These results are consistent with the view that a persistent preponderance of Th1 cells and not the mere presence of autoreactive cells determines whether or not clinically manifest CsA-AI will occur.

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Section: Discussioncontrasting

confidence: 79%

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Beijleveld

Groen

Broeren

et al. 1996

Clinical and Experimental Immunology

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“…At this point, it is likely that positive, as well as negative, selection is blocked. This inference is supported by the presence of a markedly increased proportion of DP thymocytes that express TdT (10,25) and CD53 (our unpublished observation), a marker that is down-regulated during positive selection (26). Therefore, it seems probable that autoeffector thymocytes are no longer formed after the first week of CSA treatment.…”

Section: Figurementioning

confidence: 68%

“…3). Therefore, they resembled the bulk of RTEs that are released during the first week of CSA treatment (9,10). However, by day 10 of CSA treatment, some of the autoeffector T cells appeared to have acquired a CD8-SP phenotype, as evidenced by their presence in the CD4-depleted T cell fraction; and by day 4 after CSA treatment, virtually all of the autoeffector T cells in LN were CD8 SP, as shown by their absence from the CD4-enriched T cell fraction.…”

Section: Phenotypes Of Autoeffector and Immunoregulatory T Cells In Pmentioning

confidence: 99%

Tolerance to Cyclosporin A-Induced Autologous Graft-Versus-Host Disease Is Mediated by a CD4+CD25+ Subset of Recent Thymic Emigrants

Goldschneider

2001

The Journal of Immunology

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Our previous studies revealed that both the autoeffector and immunoregulatory T cells in cyclosporin A (CSA)-induced autologous graft-vs-host disease are recent thymic emigrants (RTEs). The autoeffector cells appear in and are released from the thymus during the first week of CSA treatment, whereas the immunoregulatory thymocytes appear during the second week but are not released until several days after cessation of CSA treatment. In the present study, the antigenic phenotypes of these functional T cell subsets were determined by immunomagnetic separation and flow immunocytometric analysis. During CSA wk 1, the autoeffector T cells in both the thymus and lymph node (LN) expressed a CD4+8+ double-positive (DP) phenotype, after which those in the LN became CD8 single positive (SP). Timed thymectomy experiments confirmed that the CD8-SP autoeffector T cells in LN originated from these DP RTEs. During CSA wk 2, the immunoregulatory thymocytes also displayed a DP phenotype. However, they were not exported to the periphery until several days after CSA treatment had been interrupted and they had acquired a CD4-SP phenotype. In LN, these immunoregulatory RTEs expressed the CD25+ marker characteristic of anergic/suppressor T cells. Cell separation and mixing experiments demonstrated that the autoeffector T cells persist in LN after cessation of CSA treatment, but their activity is not detectable in the presence of recently exported CD4+ T cells. Hence, the results indicate that tolerance to CSA-induced autologous graft-vs-host disease is actively mediated by CD25+CD4+ RTEs that suppress the function of CD8 autoeffector T cells.

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“…OX-62 (rat DC) was a generous gift donated by M.J. Puklavec (Serotec, Oxford, UK). Double immunofluorescence staining was performed as previously described (Chen-Woan and Goldschneider, 1991) and 10 4 gated events were analysed for each sample on an Epics Elite flow cytometer (Coulter, Hialeah, FL).…”

Section: Immunofluorescence Labelling and Facs Analysismentioning

confidence: 99%

A new protocol for the propagation of dendritic cells from rat bone marrow using recombinant GM-CSF, and their quantification using the mAb OX-62

Chen-Woan

Delaney

Fournier

et al. 1995

Journal of Immunological Methods

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Bone marrow (BM)-derived dendritic cells (DC) are the most potent known antigen (Ag) presenting cell in vivo and in vitro. Detailed analysis of their properties and mechanisms of action requires an ability to produce large numbers of DC. Although DC have been isolated from several rat tissues, including BM, the yield is uniformly low. We describe a simple method for the propagation of large numbers of DC from rat BM and document cell yield with the rat DC marker, OX-62.After depletion of plastic-adherent and Fc + cells by panning on dishes coated with normal serum, residual BM cells were cultured in gelatin coated flasks using murine rGM-CSF supplemented medium. Prior to analysis, non-adherent cells were re-depleted of contaminating Fc + cells. Propagation of DC was monitored by double staining for FACS analysis (major histocompatibility complex (MHC) class II + /OX-62 + , OX-19 − ). Functional assay, morphological analysis and evaluation of homing patterns of cultured cells revealed typical DC characteristics. MHC class II and OX-62 antigen expression increased with time in culture and correlated with allostimulatory ability. DC yield increased until day 7, when 3.3 × 10 6 DC were obtained from an initial 3 × 10 8 unfractionated BM cells. Significant numbers of DC can be generated from rat BM using these simple methods. This should permit analysis and manipulation of rat DC functions in vivo and in vitro.

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Evidence That Cyclosporine Treatment Causes the Appearance in Rat Lymph Node of T Cells Having the Antigenic Phenotypes of Cortical Thymocytesnode

Cited by 16 publications

References 0 publications

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Susceptibility to clinically manifest cyclosporine A (CsA)-induced autoimmune disease is associated with interferon-gamma (IFN-γ)-producing CD45RC+RT6− T helper cells

Tolerance to Cyclosporin A-Induced Autologous Graft-Versus-Host Disease Is Mediated by a CD4+CD25+ Subset of Recent Thymic Emigrants

A new protocol for the propagation of dendritic cells from rat bone marrow using recombinant GM-CSF, and their quantification using the mAb OX-62

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