Volume 37, Issue 3, Pages (September 2012)

Slides:



Advertisements
Similar presentations
Figure 2. Positive selection of J15 TCR transgenic T cells specific for H60. (A) CD4 by CD8 profiles (left) of thymocytes and numbers (right) of each thymic.
Advertisements

Volume 36, Issue 3, Pages (March 2012)
Transforming Growth Factor-β Signaling Curbs Thymic Negative Selection Promoting Regulatory T Cell Development  Weiming Ouyang, Omar Beckett, Qian Ma,
Volume 43, Issue 4, Pages (October 2015)
Volume 33, Issue 6, Pages (December 2010)
Volume 47, Issue 1, Pages e8 (July 2017)
Volume 43, Issue 3, Pages (September 2015)
Generalized Resistance to Thymic Deletion in the NOD Mouse
Volume 5, Issue 5, Pages (November 1996)
Volume 29, Issue 6, Pages (December 2008)
Volume 28, Issue 2, Pages (February 2008)
Cellular Mechanisms of Fatal Early-Onset Autoimmunity in Mice with the T Cell-Specific Targeting of Transforming Growth Factor-β Receptor  Julien C. Marie,
Volume 41, Issue 2, Pages (August 2014)
Volume 31, Issue 1, Pages (July 2009)
Volume 36, Issue 1, Pages (January 2012)
Volume 43, Issue 4, Pages (October 2015)
Volume 28, Issue 2, Pages (February 2008)
Volume 33, Issue 4, Pages (October 2010)
B-1a and B-1b Cells Exhibit Distinct Developmental Requirements and Have Unique Functional Roles in Innate and Adaptive Immunity to S. pneumoniae  Karen.
Volume 7, Issue 4, Pages (October 1997)
Volume 40, Issue 2, Pages (February 2014)
Volume 21, Issue 3, Pages (September 2004)
Generalized Resistance to Thymic Deletion in the NOD Mouse
The Cellular Mechanism of Aire Control of T Cell Tolerance
Volume 33, Issue 1, Pages (July 2010)
Volume 27, Issue 5, Pages (November 2007)
Volume 36, Issue 3, Pages (March 2012)
Volume 31, Issue 3, Pages (September 2009)
Volume 29, Issue 2, Pages (August 2008)
Saskia Hemmers, Alexander Y. Rudensky  Cell Reports 
Volume 29, Issue 6, Pages (December 2008)
Volume 37, Issue 1, Pages (July 2012)
Volume 41, Issue 2, Pages (August 2014)
Volume 27, Issue 3, Pages (September 2007)
Volume 43, Issue 5, Pages (November 2015)
Volume 37, Issue 4, Pages (October 2012)
Volume 27, Issue 5, Pages (November 2007)
Volume 41, Issue 3, Pages (September 2014)
Volume 33, Issue 4, Pages (October 2010)
Volume 37, Issue 3, Pages (September 2012)
Volume 37, Issue 5, Pages (November 2012)
Volume 32, Issue 5, Pages (May 2010)
Volume 44, Issue 5, Pages (May 2016)
Volume 43, Issue 5, Pages (November 2015)
Volume 39, Issue 1, Pages (July 2013)
Volume 29, Issue 5, Pages (November 2008)
T Cells with Low Avidity for a Tissue-Restricted Antigen Routinely Evade Central and Peripheral Tolerance and Cause Autoimmunity  Dietmar Zehn, Michael.
Volume 31, Issue 4, Pages (October 2009)
Volume 25, Issue 4, Pages (October 2006)
Volume 38, Issue 3, Pages (March 2013)
Cell-Intrinsic IL-27 and gp130 Cytokine Receptor Signaling Regulates Virus-Specific CD4+ T Cell Responses and Viral Control during Chronic Infection 
Volume 37, Issue 5, Pages (November 2012)
Volume 21, Issue 1, Pages (October 2017)
Volume 41, Issue 4, Pages (October 2014)
Volume 34, Issue 3, Pages (March 2011)
Volume 42, Issue 5, Pages (May 2015)
Volume 33, Issue 5, Pages (November 2010)
SAP Protein-Dependent Natural Killer T-like Cells Regulate the Development of CD8+ T Cells with Innate Lymphocyte Characteristics  Mihalis Verykokakis,
Volume 42, Issue 6, Pages (June 2015)
Volume 21, Issue 1, Pages (October 2017)
Volume 25, Issue 4, Pages (April 2017)
Volume 25, Issue 1, Pages (July 2006)
Volume 30, Issue 2, Pages (February 2009)
Volume 27, Issue 5, Pages (November 2007)
Volume 23, Issue 4, Pages (October 2005)
Volume 22, Issue 3, Pages (March 2005)
Volume 29, Issue 3, Pages (September 2008)
Volume 33, Issue 2, Pages (August 2010)
Volume 25, Issue 4, Pages (October 2006)
Volume 2, Issue 6, Pages (December 2012)
Presentation transcript:

Volume 37, Issue 3, Pages 451-462 (September 2012) The BH3-Only Proteins Bim and Puma Cooperate to Impose Deletional Tolerance of Organ-Specific Antigens  Daniel H.D. Gray, Fiona Kupresanin, Stuart P. Berzins, Marco J. Herold, Lorraine A. O'Reilly, Philippe Bouillet, Andreas Strasser  Immunity  Volume 37, Issue 3, Pages 451-462 (September 2012) DOI: 10.1016/j.immuni.2012.05.030 Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 1 Compound Loss of Bim and Other BH3-Only Proteins Can Cause Organ-Specific Autoimmune Disease (A) H&E-stained sections of tissues from lethally irradiated Rag1−/− mice reconstituted with hematopoietic precursors from WT or Vav-BCL-2-transgenic mice, or mice lacking the indicated BH3-only proteins. Arrows indicate areas of lymphocytic infiltration. (B) Immunofluorescent staining of Rag1−/− mouse tissues with serum from Rag1−/− mice reconstituted with hematopoietic precursors from WT or Vav-BCL-2-transgenic mice, or mice lacking the indicated BH3-only proteins. Autoantibody reactivity is shown in green and nuclear DAPI staining in blue. Images are representative of n = 4 mice per group. KO, knockout; DKO, double knockout; ND, no data. Immunity 2012 37, 451-462DOI: (10.1016/j.immuni.2012.05.030) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 2 Spontaneous Organ-Specific Autoimmunity in Bbc3−/−Bcl2l11−/− Mice (A) Graph of the cumulative clinical scores of ten organs quantifying autoimmune infiltration and destruction in aged mice deficient in the proteins indicated. Groups were compared using an ANOVA with a multiple-comparison Tukey's post hoc test. ∗p < 0.05, ∗∗∗p < 0.001. Mean ages at time of analysis were: Aire−/−, 237 days (d237) (n = 11); Pmaip1−/−, d147 (n = 9); Bad−/−, d165 (n = 7); Bcl2l11−/−, d141 (n = 8); Bad−/−Bcl2l11−/−, d166 (n = 5); Pmaip1−/−Bcl2l11−/−, d153 (n = 13); and Bbc3−/−Bcl2l11−/−, d143 (n = 15). (B) Representative images of H&E-stained sections of tissues taken from aged Bbc3−/−Bcl2l11−/− mice, with arrows indicating lymphocytic infiltration. (C) Images of H&E-stained sections of pancreas taken from Rag1−/− mice that had been injected with T cells from WT or healthy Bbc3−/−Bcl2l11−/− mice. (D) Graph of the incidence and severity of pancreatitis in Rag1−/− mice that had been injected with T cells from WT or Bbc3−/−Bcl2l11−/− mice (n = 8). (E) CD44 versus CD62L expression on CD4+ splenic T cells, with the mean proportion of activated CD44hiCD62Llo/− T cells shown. Immunity 2012 37, 451-462DOI: (10.1016/j.immuni.2012.05.030) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 3 Only the Additional Loss of Puma Exacerbates Defects in Thymocyte Development in Bim-Deficient Mice (A) CD4 versus CD8 expression profiles of thymocytes from lethally irradiated mice reconstituted with hematopoietic progenitors lacking the BH3-only proteins indicated and analyzed 8 weeks later. Profiles are representative of four experiments (total n = 6–13). TKO, triple knockout. (B) Thymocyte subset proportions in mice reconstituted with hematopoietic progenitors from mice lacking the BH3-only proteins indicated (means ± SEM). Statistically significant differences among the proportions of DP thymocytes are shown, tested with a one-way ANOVA with multiple-comparison Tukey's post hoc test (∗∗∗p < 0.0001). (C) CD5 versus CD69 expression on DP thymocytes with the mean (± SEM) proportion of CD69+CD5hi thymocytes shown. (D) CD69 versus CD24 expression on CD4SP thymocytes with the mean (± SEM) proportion of mature CD69−CD24lo/− thymocytes shown. (E) Qa2 versus CD24 expression on CD4SP thymocytes with the mean (± SEM) proportion of mature Qa2+CD24lo/− thymocytes shown. (F) Graph of the numbers of FITC+ recent thymic emigrant (RTE) cells recovered from the spleens of mice 24 hr after intrathymic FITC injection, with means ± SEM shown. Immunity 2012 37, 451-462DOI: (10.1016/j.immuni.2012.05.030) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 4 Bim and Puma Are Required for Deletion of OT-I Thymocytes in RIP-mOVA+ Mice (A) Representative dot plots of CD4 and CD8 expression gated on H2-Kb-OVA tetramer+ thymocytes from WT or RIP-mOVA+ chimeras that had been reconstituted with BM from OT-I transgenic mice on WT, Bim-deficient, or Puma- and Bim-double-deficient backgrounds. The percentages of DP, CD4SP, and CD8SP gated on H2-Kb-OVA+ thymocytes are shown. (B and C) Mean percentages (B) and cell numbers (C) of H2-Kb-OVA+ CD8SP thymocytes (± SEM) from the various chimeras. (D) H2-Kb-OVA versus CD8 staining on splenocytes from the various chimeras, with the proportion of H2-Kb-OVA+ CD8+ T cells shown. (E and F) Mean percentages (E) and numbers (F) of H2-Kb-OVA+ CD8+ splenocytes (± SEM) from the various chimeras. PB denotes Puma and Bim double deficient. Groups composed of three to four mice were compared using Student's t test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Data from one of two experiments are shown. Immunity 2012 37, 451-462DOI: (10.1016/j.immuni.2012.05.030) Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 5 Both Bim and Puma Are Required for the Deletion of Mature CD4SP OT-II Thymocytes in RIP-mOVA+ Mice (A) Representative dot plots of CD4 and CD8 expression gated on Vα2/Vβ5+ thymocytes from RIP-mOVA− or RIP-mOVA+ chimeras that had been reconstituted with BM from OT-II transgenic mice on WT, Bim-deficient, or Puma- and Bim-double-deficient backgrounds. The percentages of Vα2/Vβ5+ CD4SP thymocytes are shown. (B and C) Mean percentages and cell numbers of Vα2/Vβ5+ CD4SP thymocytes (B) or Vα2/Vβ5+CD4+ splenocytes (C) (± SEM) from the various chimeras. (D) CD24 versus Qa2 expression on Vα2/Vβ5+ CD4SP thymocytes from the various chimeras. Groups composed of three to four mice were compared using Student's t test; ∗p < 0.05, ∗∗p < 0.01. Data from one of two experiments are shown. Immunity 2012 37, 451-462DOI: (10.1016/j.immuni.2012.05.030) Copyright © 2012 Elsevier Inc. Terms and Conditions