Skip to main content

Advertisement

SpringerLink
Log in

In vasculitis of small muscular arteries, activation of vessel-infiltrating CD8 T cells seems to be antigen-independent

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The etiology of polyarteritis nodosa (PAN) and localized PAN is still unknown, although a T cell-mediated immune mechanism has been considered. CD8 T cells participate not only in the antigen-dependent adaptive immune system, but also in the antigen-independent innate immune system. Non-antigen-activated CD8 T cells express a unique phenotype: granzyme B (GrB) positive /CD25 negative /programmed death-1 (PD-1) negative. The aims of this study were to assess the participation of T cells, especially innate CD8 T cells, in the development of vasculitis. Twenty-eight consecutive cases of skin biopsy specimens with cutaneous vasculitis of small muscular arteries (CVSMA) were retrieved. The series comprises of 21 cases of cutaneous arteritis, three cases of PAN, and four cases of rheumatoid vasculitis. Cases of antineutrophil cytoplasmic antibody-associated vasculitis were excluded. The phenotypes of infiltrating lymphocytes in vasculitis lesions were evaluated by immunohistochemistry. In most cases of CVSMA, the number of CD8 T cells infiltrating the intima was higher than that of CD4 T cells, and significant numbers of GrB-positive cells, which represent activated CD8 T cells, were observed. However, GrB/CD25-double-positive cells, which correspond to antigen-activated T cells, were very few in a small number of cases. Cells positive for PD-1, which is also expressed on antigen-activated CD8 T cells, were not detected. We conclude that a T cell-mediated immune mechanism, involving cytotoxic CD8 T cells, may play a role in the development of CVSMA. Low expression of CD25 in activated CD8 T cells suggests that activation was antigen-independent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Matsumoto T, Kobayashi S, Ogishima D, Aoki Y, Sonoue H, Abe H, Fukumura Y, Nobukawa B, Kumasaka T, Mori S, Suda K (2007) Isolated necrotizing arteritis (localized polyarteritis nodosa): examination of the histological process and disease entity based on the histological classification of stage and histological differences from polyarteritis nodosa. Cardiovascular Pathology : Official J Soc Cardiovascular Pathology 16(2):92–97. https://doi.org/10.1016/j.carpath.2006.09.005

    Article  Google Scholar 

  2. Cid MC, Grau JM, Casademont J, Campo E, Coll-Vinent B, López-Soto A, Ingelmo M, Urbano-Márquez A (1994) Immunohistochemical characterization of inflammatory cells and immunologic activation markers in muscle and nerve biopsy specimens from patients with systemic polyarteritis nodosa. Arthritis Rheum 37(7):1055–1061

    Article  CAS  PubMed  Google Scholar 

  3. Kissel JT, Riethman JL, Omerza J, Rammohan KW, Mendell JR (1989) Peripheral nerve vasculitis: immune characterization of the vascular lesions. Ann Neurol 25(3):291–297. https://doi.org/10.1002/ana.410250314

    Article  CAS  PubMed  Google Scholar 

  4. Gurer G, Erdem S, Kocaefe Ç, Özgüç M, Tan E (2004) Expression of matrix metalloproteinases in vasculitic neuropathy. Rheumatol Int 24(5):255–259. https://doi.org/10.1007/s00296-003-0380-6

    Article  CAS  PubMed  Google Scholar 

  5. Freeman BE, Hammarlund E, Raué HP, Slifka MK (2012) Regulation of innate CD8+ T-cell activation mediated by cytokines. Proc Natl Acad Sci U S A 109(25):9971–9976. https://doi.org/10.1073/pnas.1203543109

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Tietze JK, Wilkins DEC, Sckisel GD, Bouchlaka MN, Alderson KL, Weiss JM, Ames E, Bruhn KW, Craft N, Wiltrout RH, Longo DL, Lanier LL, Blazar BR, Redelman D, Murphy WJ (2012) Delineation of antigen-specific and antigen-nonspecific CD8(+) memory T-cell responses after cytokine-based cancer immunotherapy. Blood 119(13):3073–3083. https://doi.org/10.1182/blood-2011-07-369736

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, Flores-Suarez LF, Gross WL, Guillevin L, Hagen EC, Hoffman GS, Jayne DR, Kallenberg CGM, Lamprecht P, Langford CA, Luqmani RA, Mahr AD, Matteson EL, Merkel PA, Ozen S, Pusey CD, Rasmussen N, Rees AJ, Scott DG, Specks U, Stone JH, Takahashi K, Watts RA (2013) 2012 revised international chapel hill consensus conference nomenclature of vasculitides. Arthritis Rheum 65(1):1–11. https://doi.org/10.1002/art.37715

    Article  CAS  PubMed  Google Scholar 

  8. Arkin A (1930) A clinical and pathological study of periarteritis nodosa: a report of five cases, one histologically healed. Am J Pathol 6:401–426

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Ishibashi M, Chen KR (2008) A morphological study of evolution of cutaneous polyarteritis nodosa. Am J Dermatopathol 30(4):319–326. https://doi.org/10.1097/DAD.0b013e3181766190

    Article  PubMed  Google Scholar 

  10. Oudejans JJ, Jiwa NM, Kummer JA, Horstman A, Vos W, Baak JP, Kluin PM, van der Valk P, Walboomers JM, Meijer CJ (1996) Analysis of major histocompatibility complex class I expression on Reed-Sternberg cells in relation to the cytotoxic T-cell response in Epstein-Barr virus-positive and -negative Hodgkin’s disease. Blood 87(9):3844–3851

    CAS  PubMed  Google Scholar 

  11. Coll-Vinent B, Cebrián M, Cid MC, Font C, Esparza J, Juan M, Yagüe J, Urbano-Márquez A, Grau JM (1998) Dynamic pattern of endothelial cell adhesion molecule expression in muscle and perineural vessels from patients with classic polyarteritis nodosa. Arthritis Rheum 41(3):435–444. https://doi.org/10.1002/1529-0131(199803)41:3<435::AID-ART9>3.0.CO;2-9

    Article  CAS  PubMed  Google Scholar 

  12. Yusuf-Makagiansar H, Anderson ME, Yakovleva TV, Murray JS, Siahaan TJ (2002) Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases. Med Res Rev 22(2):146–167

    Article  CAS  PubMed  Google Scholar 

  13. Iinuma C, Waki M, Kawakami A, Yamaguchi M, Tomaru U, Sasaki N, Masuda S, Matsui Y, Iwasaki S, Baba T, Kasahara M, Yoshiki T, Paletta D, Herrmann T, Ishizu A (2015) Establishment of a vascular endothelial cell-reactive type II NKT cell clone from a rat model of autoimmune vasculitis. Int Immunol 27(2):105–114. https://doi.org/10.1093/intimm/dxu088

    Article  CAS  PubMed  Google Scholar 

  14. Sckisel GD, Tietze JK, Zamora AE, Hsiao HH, Priest SO, Wilkins DEC, Lanier LL, Blazar BR, Baumgarth N, Murphy WJ (2014) Influenza infection results in local expansion of memory CD8(+) T cells with antigen non-specific phenotype and function. Clin Exp Immunol 175(1):79–91. https://doi.org/10.1111/cei.12186

    Article  CAS  PubMed  Google Scholar 

  15. Lertmemongkolchai G, Cai G, Hunter CA, Bancroft GJ (2001) Bystander activation of CD8+ T cells contributes to the rapid production of IFN-gamma in response to bacterial pathogens. J Immunol 166(2):1097–1105

    Article  CAS  PubMed  Google Scholar 

  16. Suarez-Ramirez JE, Tarrio ML, Kim K, Demers DA, Biron CA (2014) CD8 T cells in innate immune responses: using STAT4-dependent but antigen-independent pathways to gamma interferon during viral infection. mBio 5(5):e01978–e01914. https://doi.org/10.1128/mBio.01978-14

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, Bienvenu B, Mouthon L, Guillevin L (2010) Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum 62(2):616–626. https://doi.org/10.1002/art.27240

    Article  PubMed  Google Scholar 

  18. Pryshchep O, Ma-Krupa W, Younge BR, Goronzy JJ, Weyand CM (2008) Vessel-specific Toll-like receptor profiles in human medium and large arteries. Circulation 118(12):1276–1284. https://doi.org/10.1161/CIRCULATIONAHA.108.789172

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Marchi LF, Sesti-Costa R, Ignacchiti MDC, Chedraoui-Silva S, Mantovani B (2014) In vitro activation of mouse neutrophils by recombinant human interferon-gamma: increased phagocytosis and release of reactive oxygen species and pro-inflammatory cytokines. Int Immunopharmacol 18(2):228–235. https://doi.org/10.1016/j.intimp.2013.12.010

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Ms. Tomoko Nishizawa and Mr. Masanobu Momose for technical assistance.

Funding

This work was supported in part by grant from Research on Rare and Intractable Diseases, the Ministry of Health, Labor and Welfare of Japan (nannchi-ippann-044).

Author information

Authors and Affiliations

  1. Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Mikiko Kobayashi & Hiroyuki Kanno

  2. Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Eisaku Ogawa & Ryuhei Okuyama

Authors
  1. Mikiko Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eisaku Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryuhei Okuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroyuki Kanno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Kanno.

Ethics declarations

This study was approved by the ethics committee of Shinshu University School of Medicine, Japan.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kobayashi, M., Ogawa, E., Okuyama, R. et al. In vasculitis of small muscular arteries, activation of vessel-infiltrating CD8 T cells seems to be antigen-independent. Virchows Arch 472, 271–279 (2018). https://doi.org/10.1007/s00428-017-2264-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2264-2

Keywords

Search

Navigation