Supplementary Figure 1: Long Term Appearance of Accepted Lung Grafts. (A) Gross Appearance

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Supplementary Figure 1: Long Term Appearance of Accepted Lung Grafts. (A) Gross Appearance

Supplementary Figure 1: Long term appearance of accepted lung grafts. (a) Gross appearance of Balb/c lung allograft 13 months after transplantation into immunosuppressed (MR1, CTLA4-Ig) B6 recipient (Tx depicts transplanted graft). (b)

Histological appearance of native B6 right lung and (c) BALT in Balb/c allograft 7 months after transplantation into immunosuppressed (MR1, CTLA4-Ig) B6 recipient

(100x). (d) represents a zoomed view of BALT shown in (c) (200x).

Supplementary Figure 2: Appearance of immunosuppressed heart grafts. Two-photon image of dendritic cells in (a) heart explants derived from resting B6 CD11c + EYFP mice and (b) Balb/c heart graft explants 30 days after transplantation into immunosuppressed

(MR1, CTLA4-Ig) B6 CD11c+ EYFP recipients. Scale bar = 20 µm. (c) Immunostaining

(100x) for PNAd for B6 heart grafts 30 days after transplantation into immunosuppressed (MR1, CTLA4-Ig) CBA hosts.

Supplementary Figure 3: PD-L1 expression on dendritic cells in BALT of accepted lung allografts. (a) Flow cytometric analysis of PD-L1 expression on myeloid dendritic cells

(CD11c+CD11bhi) in accepted B6 lung allografts 30 days after transplantation into immunosuppressed (MR1, CTLA4-Ig) CBA recipients (n=3) Shaded histogram depicts staining with isotype control antibody. (b) Immunofluorescent staining showing expression of PD-L1 (red) on CD11c+ dendritic cells (green) within BALT of accepted

Balb/c lung allografts 30 days after transplantation into immunosuppressed (MR1,

CTLA4-Ig) B6 CD11c-EYFP hosts.

1 Supplementary Movie 1: Intravital two-photon imaging of dendritic cells (green) within

BALT in accepted Balb/c lung grafts 30 days after transplantation into immunosuppressed (MR1 250 µg i.p. day 0, CTLA4-Ig 200 µg i.p. day 2) B6 CD11c+

EYFP recipients. Relative time is displayed in hrs:min:sec:msec.

Supplementary Movie 2: Intravital two-photon imaging of adoptively transferred

CMTMR-labeled B6 T lymphocytes (yellow) with dendritic cells (green) within BALT in accepted Balb/c lung grafts 30 days after transplantation into immunosuppressed (MR1

250 µg i.p. day 0, CTLA4-Ig 200 µg i.p. day 2) B6 CD11c + EYFP recipients. Collagen and alveolar macrophages appear blue (second harmonic generation) and blood vessels appear red. Relative time is displayed in hrs:min:sec:msec.

2 References

1. Kreisel, D., et al. Short- and long-term outcomes of 1000 adult lung transplant recipients

at a single center. J Thorac Cardiovasc Surg 141, 215-222 (2011).

2. Khalifah, A.P., et al. Minimal acute rejection after lung transplantation: a risk for

bronchiolitis obliterans syndrome. Am J Transplant 5, 2022-2030 (2005).

3. Prop, J., Tazelaar, H.D. & Billingham, M.E. Rejection of combined heart-lung transplants

in rats. Function and pathology. The American Journal of Pathology 127, 97-105 (1987).

4. McGregor, C.G., et al. Combined heart-lung transplantation for end-stage Eisenmenger's

syndrome. J Thorac Cardiovasc Surg 91, 443-450 (1986).

5. Gelman, A.E., et al. Cutting edge: Acute lung allograft rejection is independent of

secondary lymphoid organs. J Immunol 182, 3969-3973 (2009).

6. Lakkis, F.G., Arakelov, A., Konieczny, B.T. & Inoue, Y. Immunologic 'ignorance' of

vascularized organ transplants in the absence of secondary lymphoid tissue. Nat Med 6,

686-688 (2000).

7. Lechler, R.I. & Batchelor, J.R. Immunogenicity of retransplanted rat kidney allografts.

Effect of inducing chimerism in the first recipient and quantitative studies on

immunosuppression of the second recipient. J Exp Med 156, 1835-1841 (1982).

8. Graca, L., Cobbold, S.P. & Waldmann, H. Identification of regulatory T cells in tolerated

allografts. J Exp Med 195, 1641-1646 (2002).

9. Marui, T., et al. Histologic damage of lung allografts according to magnitude of acute

rejection in the re-isotransplant model. J Heart Lung Transplant 27, 642-648 (2008).

3 10. Tullius, S.G., et al. Contribution of early acute rejection episodes to chronic rejection in a

rat kidney retransplantation model. Kidney Int 53, 465-472 (1998).

11. Izutani, H., et al. Evidence that graft coronary arteriosclerosis begins in the early phase

after transplantation and progresses without chronic immunoreaction. Histopathological

analysis using a retransplantation model. Transplantation 60, 1073-1079 (1995).

12. Gelman, A.E., et al. CD4+ T lymphocytes are not necessary for the acute rejection of

vascularized mouse lung transplants. J Immunol 180, 4754-4762 (2008).

13. Okazaki, M., et al. Maintenance of airway epithelium in acutely rejected orthotopic

vascularized mouse lung transplants. Am J Respir Cell Mol Biol 37, 625-630 (2007).

14. Okazaki, M., et al. Costimulatory blockade-mediated lung allograft acceptance is

abrogated by overexpression of Bcl-2 in the recipient. Transplant Proc 41, 385-387

(2009).

15. Moyron-Quiroz, J.E., et al. Role of inducible bronchus associated lymphoid tissue

(iBALT) in respiratory immunity. Nature Medicine 10, 927-934 (2004).

16. Rangel-Moreno, J., et al. Inducible bronchus-associated lymphoid tissue (iBALT) in

patients with pulmonary complications of rheumatoid arthritis. The Journal of Clinical

Investigation 116, 3183-3194 (2006).

17. Randall, T.D. Bronchus-associated lymphoid tissue (BALT) structure and function.

Advances in Immunology 107, 187-241 (2010).

18. Kreisel, D., et al. In vivo two-photon imaging reveals monocyte-dependent neutrophil

extravasation during pulmonary inflammation. Proc Natl Acad Sci U S A 107, 18073-

18078 (2010).

4 19. Lindquist, R.L., et al. Visualizing dendritic cell networks in vivo. Nat Immunol 5, 1243-

1250 (2004).

20. Gelman, A.E., et al. CCR2 regulates monocyte recruitment as well as CD4 T1

allorecognition after lung transplantation. Am J Transplant 10, 1189-1199 (2010).

21. Samy, E.T., Wheeler, K.M., Roper, R.J., Teuscher, C. & Tung, K.S. Cutting edge:

Autoimmune disease in day 3 thymectomized mice is actively controlled by endogenous

disease-specific regulatory T cells. J Immunol 180, 4366-4370 (2008).

22. Setiady, Y.Y., Coccia, J.A. & Park, P.U. In vivo depletion of CD4+FOXP3+ Treg cells by

the PC61 anti-CD25 monoclonal antibody is mediated by FcgammaRIII+ phagocytes.

Eur J Immunol 40, 780-786 (2010).

23. Loebbermann, J., et al. Regulatory T cells expressing granzyme B play a critical role in

controlling lung inflammation during acute viral infection. Mucosal Immunology 5, 161-

172 (2012).

24. Zhang, N., et al. Regulatory T cells sequentially migrate from inflamed tissues to

draining lymph nodes to suppress the alloimmune response. Immunity 30, 458-469

(2009).

25. Constant, S.L., et al. Resident lung antigen-presenting cells have the capacity to promote

Th2 T cell differentiation in situ. J Clin Invest 110, 1441-1448 (2002).

26. Aloisi, F. & Pujol-Borrell, R. Lymphoid neogenesis in chronic inflammatory diseases.

Nat Rev Immunol 6, 205-217 (2006).

27. Grant, A.J., et al. Hepatic expression of secondary lymphoid chemokine (CCL21)

promotes the development of portal-associated lymphoid tissue in chronic inflammatory

liver disease. The American Journal of Pathology 160, 1445-1455 (2002).

5 28. Barone, F., et al. Association of CXCL13 and CCL21 expression with the progressive

organization of lymphoid-like structures in Sjogren's syndrome. Arthritis Rheum 52,

1773-1784 (2005).

29. Thaunat, O., et al. Lymphoid neogenesis in chronic rejection: evidence for a local

humoral alloimmune response. Proceedings of the National Academy of Sciences of the

United States of America 102, 14723-14728 (2005).

30. Wang, J., et al. Donor lymphoid organs are a major site of alloreactive T-cell priming

following intestinal transplantation. Am J Transplant 6, 2563-2571 (2006).

31. Baddoura, F.K., et al. Lymphoid neogenesis in murine cardiac allografts undergoing

chronic rejection. Am J Transplant 5, 510-516 (2005).

32. Nasr, I.W., et al. Tertiary lymphoid tissues generate effector and memory T cells that

lead to allograft rejection. Am J Transplant 7, 1071-1079 (2007).

33. Brown, K., Sacks, S.H. & Wong, W. Tertiary lymphoid organs in renal allografts can be

associated with donor-specific tolerance rather than rejection. European Journal of

Immunology 41, 89-96 (2011).

34. Sminia, T., van der Brugge-Gamelkoorn, G.J. & Jeurissen, S.H. Structure and function of

bronchus-associated lymphoid tissue (BALT). Critical Reviews in Immunology 9, 119-

150 (1989).

35. Moyron-Quiroz, J.E., et al. Persistence and responsiveness of immunologic memory in

the absence of secondary lymphoid organs. Immunity 25, 643-654 (2006).

36. van der Strate, B.W., et al. Cigarette smoke-induced emphysema: A role for the B cell?

Am J Respir Crit Care Med 173, 751-758 (2006).

6 37. Sato, M., et al. The role of intrapulmonary de novo lymphoid tissue in obliterative

bronchiolitis after lung transplantation. J Immunol 182, 7307-7316 (2009).

38. Hasegawa, T., Iacono, A. & Yousem, S.A. The significance of bronchus-associated

lymphoid tissue in human lung transplantation: is there an association with acute and

chronic rejection? Transplantation 67, 381-385 (1999).

39. Francisco, L.M., et al. PD-L1 regulates the development, maintenance, and function of

induced regulatory T cells. J Exp Med 206, 3015-3029 (2009).

40. Krupnick, A.S., et al. Murine vascular endothelium activates and induces the generation

of allogeneic CD4+25+Foxp3+ regulatory T cells. J Immunol 175, 6265-6270 (2005).

41. Wolfle, S.J., et al. PD-L1 expression on tolerogenic APCs is controlled by STAT-3. Eur

J Immunol 41, 413-424 (2011).

42. Halle, S., et al. Induced bronchus-associated lymphoid tissue serves as a general priming

site for T cells and is maintained by dendritic cells. J Exp Med 206, 2593-2601 (2009).

43. Mempel, T.R., Henrickson, S.E. & Von Andrian, U.H. T-cell priming by dendritic cells

in lymph nodes occurs in three distinct phases. Nature 427, 154-159 (2004).

44. Miller, M.J., Safrina, O., Parker, I. & Cahalan, M.D. Imaging the single cell dynamics of

CD4+ T cell activation by dendritic cells in lymph nodes. The Journal of Experimental

Medicine 200, 847-856 (2004).

45. Rangel-Moreno, J., Moyron-Quiroz, J.E., Hartson, L., Kusser, K. & Randall, T.D.

Pulmonary expression of CXC chemokine ligand 13, CC chemokine ligand 19, and CC

chemokine ligand 21 is essential for local immunity to influenza. Proceedings of the

National Academy of Sciences of the United States of America 104, 10577-10582 (2007).

7 46. Okazaki, M., et al. A mouse model of orthotopic vascularized aerated lung

transplantation. Am J Transplant 7, 1672-1679 (2007).

47. Krupnick, A.S., et al. Orthotopic mouse lung transplantation as experimental

methodology to study transplant and tumor biology. Nat Protoc 4, 86-93 (2009).

48. Tomita, Y., et al. Improved technique of heterotopic cervical heart transplantation in

mice. Transplantation 64, 1598-1601 (1997).

49. Zinselmeyer, B.H., et al. Chapter 16. Two-photon microscopy and multidimensional

analysis of cell dynamics. Methods Enzymol 461, 349-378 (2009).

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