1. Immune Control of the Cardiovascular System
David G. Harrison, M.D., Vanderbilt University School of Medicine

2. Early Studies of Immunity and Hypertension
1. White FN, Grollman A. Autoimmune factors associated with infarction of the kidney. Nephron. 1964;204:93-102
2. Okuda T, Grollman A. Passive transfer of autoimmune induced hypertension in the rat by lymph node cells. Tex Rep Biol Med. 1967;25:
3. Svendsen UG. The role of thymus for the development and prognosis of hypertension and hypertensive vascular disease in mice following renal infarction. Acta Pathol Microbiol Scand A. 1976;84:
4. Svendsen UG. Evidence for an initial, thymus independent and a chronic, thymus dependent phase of DOCA and salt hypertension in mice. Acta Pathol Microbiol Scand A. 1976;84:
5. Olsen F. Transfer of arterial hypertension by splenic cells from DOCA-salt hypertensive and renal hypertensive rats to normotensive recipients. Acta Pathol Microbiol Scand C. 1980;88:1-5

3. Reduction of Renal Injury by MMF in 5/6 Nephrectomy Model
Fig. 4, A-F.
From Tapia et al. Kidney Int ,
63:
Freely available at

4. Hypertension Induced by Aortic Coarctation Above the Renal Arteries Is Associated With Immune Cell Infiltration of the Kidneys
Fig. 3.
From Rodriguez-Iturbe et al. Am J Hypertens 2005; 18:1449–1456.
Available at

5. Mycophenolate Mofetil Treatment Improves Hypertension in Patients with Psoriasis and Rheumatoid Arthritis
Fig. 1, A & B.
From Herrera et al. J Am Soc Nephrol 2006; 17: S218-S225.
Freely available at jasn.asnjournals.org/content/17/12_suppl_3/S218.full.pdf

6. Mycophenolate Mofetil Treatment Improves Hypertension in Patients with Psoriasis and Rheumatoid Arthritis
Data from Table 3.
From Herrera et al. J Am Soc Nephrol 2006; 17: S218-S225.
Freely available at jasn.asnjournals.org/content/17/12_suppl_3/S218.full.pdf

7. Kidney in Malignant Hypertension
Figure from famous Pathology textbook – current edition,
showing normal kidney vs. kidney in malignant hypertension

8. T Cells and Hypertension
RAG1-/- mice, lacking T and B cells, exhibit blunted hypertension to Angiotensin II, DOCA-salt and norepinephrine
Fig. 1, A-C.
From Guzik et al. J Exp Med 2007; 204:
Freely available at jem.rupress.org/content/204/10/2449.full

9. Effect of Lymphocyte Adoptive Transfer on Hypertension in Rag-/- Mice
Fig. 4B (top 2 lines and bottom line).
From Guzik et al. J Exp Med 2007; 204:
Freely available at jem.rupress.org/content/204/10/2449.full
Fig. 4F.
From Marvar et al. Circ Res. 2010; 107:
Freely available at circres.ahajournals.org/content/107/2/263.full

10. Lymphocyte Responses Exacerbate Angiotensin II-Dependent Hypertension
Fig. 1, B and C.
From Crowley et al., Am J Physiol Regul Integr Comp Physiol 298: R1089–R1097, 2010.
Freely available at ajpregu.physiology.org/content/298/4/R1089.full
(Reprinted with permission)

11. Genetic Mutation of Recombination Activating Gene 1 in Dahl Salt-sensitive Rats Attenuates Hypertension and Renal Damage
Fig. 3.
From Mattson et al. Am J Physiol Regul Integr Comp Physiol 2013; 304: R407–R414.
Available at Reprinted with permission.

12. Genetic Mutation of Recombination Activating Gene 1 in Dahl Salt-sensitive Rats Attenuates Hypertension and Renal Damage
Figs. 5 and 6.
From Mattson et al. Am J Physiol Regul Integr Comp Physiol 2013; 304: R407–R414.
Available at Reprinted with permission.

13. Cytokines Mediating Hypertension and Vascular Dysfunction
Periadvential Fat
T cells
Cytokines

14. Cytokines Implicated in Hypertension
Tumor necrosis factor a
Interleukin 17
Interferon g
Interleukin 6
Tissue growth factor b
Interleukin 10

15. IL17 is Required for the Maintenance of Ang II-Induced Hypertension
Fig. 2, A & C (showing systolic BP only).
From Madhur et al. Hypertension 2010; 55:
Freely available at hyper.ahajournals.org/content/55/2/500.full

16. Ang II Increases T Cell IL17 Production and Circulating TH17 Cells
Fig. 1.
From Madhur et al. Hypertension 2010; 55:
Freely available at hyper.ahajournals.org/content/55/2/500.full

17. IL-17 Contributes to Vascular Superoxide Production in Ang II-Induced Hypertension
Fig. 4, D & E.
From Madhur et al. Hypertension 2010; 55:
Freely available at hyper.ahajournals.org/content/55/2/500.full

18. Reduced Inflammatory Response in the Vasculature of IL17-/- Mice in Response to Angiotensin II
Fig. 5, B & C.
From Madhur et al. Hypertension 2010; 55:
Freely available at hyper.ahajournals.org/content/55/2/500.full

19. IL-17 Levels in Normotensive and Hypertensive Patients with Type II DM
Table 1.
From Madhur et al. Hypertension 2010; 55:
Freely available at hyper.ahajournals.org/content/55/2/500.full

20. Interleukin-17 Causes Rho-Kinase-Mediated Endothelial Dysfunction and Hypertension
Figs. 1A and 3, A & B.
From: Nguyen et al. Cardiovasc Res 2013; 97: 696–704.
Available at cardiovascres.oxfordjournals.org/content/97/4/696.full

21. Interleukin-17 Causes Rho-Kinase-Mediated Endothelial Dysfunction and Hypertension
Figure 4B.
From Nguyen et al. Cardiovasc Res 2013; 97: 696–704.
Available at cardiovascres.oxfordjournals.org/content/97/4/696.full

22. Induction of Pathogenic TH17 Cells by Inducible Salt-Sensing Kinase SGK1
Figs. 1b, 2c & 2d (right-side).
From Wu et al. Nature 2013; 496:
Available at

23. Induction of Pathogenic TH17 Cells by Inducible Salt-Sensing Kinase SGK1
Fig. 4a.
From Wu et al. Nature 2013; 496:
Available at

24. Renal Hypertonicity and IL-17 Levels in Angiotensin II-Induced Hypertension
Figure not available; unpublished data.

25. Flow Cytometry Detection of Tc17 Cells in the Kidney
Figure not available; unpublished data.

26. Figure not available; unpublished data.

27. Tc17 Cells Mediate Renal Microvascular Remodeling in Hypertension
Figure not available; unpublished data.

28. Role of Tc17 Cells in Renal Sodium and Volume Excretion
Figure not available; unpublished data.

29. Classic Pathway for T Cell Activation – Role of Co-Stimulation
Figure not available; unpublished data.

30. Effect of CTLA4IG on Angiotensin II-Induced Hypertension
Fig. 1, C & D.
From Vinh et al. Circulation 2010; 122: 2529–2537.
Freely available at

31. Effect of CTLA4-Ig on Established DOCA-Salt Hypertension
Fig. 8B.
Vinh et al. Circulation 2010; 122: 2529–2537.
Freely available at

32. Effect of CTLA4-Ig on Established DOCA-Salt Hypertension
Fig. 5.
Vinh et al. Circulation 2010; 122: 2529–2537.
Freely available at

33. Collaborators and Contributors
Harrison Lab
Madhur Lab
Stanford
Connie Weyand
Jorg Goronzy
Annet Kirabo
Wei Chen
Salim Thabet
Hana Itani
Liang Xiao
Dan Trott
Jing Wu
Meena Madhur
Jens Titze
Mohamed Saleh
Sergey Dikalov
Sean Davies
Ken Bernstein
(Cedars Sinai)
Jack Roberts
Tom Guzik
(Cracow)
Jing Wu