Distinct Dacryoadenitides Autoadoptively Transferred to Rabbits by Different Subpopulations of Lymphocytes Activated Ex Vivo

Overview

Journal Cornea

Specialty Ophthalmology

Date 2010 Jun 26

PMID 20577087

Citations 2

Authors

Padmaja B Thomas

Deedar M Samant

Yanru Wang

Shivaram Selvam

Douglas Stevenson

John D Gray

Joel E Schechter

Austin K Mircheff

Melvin D Trousdale

Affiliations

Soon will be listed here.

Abstract

Purpose: To test whether CD4+ T cells proliferate in mixed cell reactions with autologous lacrimal gland (LG) acinar cells and whether these cells can autoadoptively transfer disease.

Methods: Purified acinar cells were gamma irradiated and cocultured with peripheral blood lymphocytes. Activated CD4+ T cells were sorted by fluorescence-activated cell sorting (FACS). Unfractionated activated peripheral blood lymphocytes (UF), CD4+-enriched and CD4+-depleted T cells from an autologous mixed cell reaction were injected into the donor rabbit's remaining LG. After 4 weeks, ocular examinations were performed, and the rabbits were euthanized; LGs were removed for histopathology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction studies.

Results: CD4 T cells increased in the autologous mixed cell reaction from 20% to 80%. Tear production decreased in the induced disease/UF (ID/UF) group and declined even more in the ID/CD4+-enriched group. Tear breakup times decreased and rose bengal staining increased in all groups. All LGs exhibited significant histopathology and increased messenger RNAs for tumor necrosis factor α. The ID/UF group exhibited the largest increases of CD4+ and rabbit T-lymphocyte antigen-positive cells. The ID/CD4+-enriched group contained fewer infiltrating CD4 cells but more eosinophils, severely altered acinar morphology, and increased fibrosis. LG of the ID/CD4+-depleted group exhibited large increases of CD18, major histocompatibility complex II, and CD4+ cells. Messenger RNAs for interleukin 2, interleukin 4, and CD4+ increased in the ID/CD4+-enriched group compared with the CD4+-depleted group.

Conclusions: Autoreactive CD4+ effector cells activated ex vivo and autoadoptively transferred, caused what seems to be a distinct dacryoadenitis. The CD4+-depleted cell fraction also contained pathogenic effector cells capable of inducing disease.

Citing Articles

Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a Rabbit Model of Induced Autoimmune Dacryoadenitis.

Li X, Lu X, Sun D, Wang X, Yang L, Zhao S Invest Ophthalmol Vis Sci. 2016; 57(13):5161-5170.

PMID: 27699412 PMC: 6016434. DOI: 10.1167/iovs.15-17824.

Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes.

Mircheff A, Wang Y, Schechter J, Li M, Tong W, Attar M Ocul Surf. 2016; 14(4):460-483.e3.

PMID: 27423911 PMC: 5065763. DOI: 10.1016/j.jtos.2016.07.001.

References

Berlo S, van Kooten P, Ten Brink C, Hauet-Broere F, Oosterwegel M, Glant T . Naive transgenic T cells expressing cartilage proteoglycan-specific TCR induce arthritis upon in vivo activation. J Autoimmun. 2005; 25(3):172-80. DOI: 10.1016/j.jaut.2005.09.017. View

Trousdale M, Zhu Z, Stevenson D, Schechter J, Ritter T, Mircheff A . Expression of TNF inhibitor gene in the lacrimal gland promotes recovery of tear production and tear stability and reduced immunopathology in rabbits with induced autoimmune dacryoadenitis. J Autoimmune Dis. 2005; 2:6. PMC: 1187915. DOI: 10.1186/1740-2557-2-6. View

Bardos T, Mikecz K, Finnegan A, Zhang J, Glant T . T and B cell recovery in arthritis adoptively transferred to SCID mice: antigen-specific activation is required for restoration of autopathogenic CD4+ Th1 cells in a syngeneic system. J Immunol. 2002; 168(12):6013-21. DOI: 10.4049/jimmunol.168.12.6013. View

Damato B, Allan D, Murray S, Lee W . Senile atrophy of the human lacrimal gland: the contribution of chronic inflammatory disease. Br J Ophthalmol. 1984; 68(9):674-80. PMC: 1040437. DOI: 10.1136/bjo.68.9.674. View

Thomas P, Zhu Z, Selvam S, Samant D, Stevenson D, Mircheff A . Autoimmune dacryoadenitis and keratoconjunctivitis induced in rabbits by subcutaneous injection of autologous lymphocytes activated ex vivo against lacrimal antigens. J Autoimmun. 2008; 31(2):116-22. PMC: 2610630. DOI: 10.1016/j.jaut.2008.04.019. View

Guo Z, Azzarolo A, Schechter J, Warren D, Wood R, Mircheff A . Lacrimal gland epithelial cells stimulate proliferation in autologous lymphocyte preparations. Exp Eye Res. 2000; 71(1):11-22. DOI: 10.1006/exer.2000.0856. View

de Saint Jean M, Nakamura T, Wang Y, Trousdale M, Schechter J, Mircheff A . Suppression of lymphocyte proliferation and regulation of dendritic cell phenotype by soluble mediators from rat lacrimal epithelial cells. Scand J Immunol. 2009; 70(1):53-62. PMC: 2712116. DOI: 10.1111/j.1365-3083.2009.02272.x. View

Maffia P, Brewer J, Gracie J, Ianaro A, Leung B, Mitchell P . Inducing experimental arthritis and breaking self-tolerance to joint-specific antigens with trackable, ovalbumin-specific T cells. J Immunol. 2004; 173(1):151-6. DOI: 10.4049/jimmunol.173.1.151. View

Takahashi M, Mimura Y, Hamano H, Haneji N, Yanagi K, Hayashi Y . Mechanism of the development of autoimmune dacryodenitis in the mouse model for primary Sjögren's syndrome. Cell Immunol. 1996; 170(1):54-62. DOI: 10.1006/cimm.1996.0133. View

10.

Ji Q, Chang L, Vandenberg D, Stanczyk F, Stolz A . Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism. Prostate. 2003; 54(4):275-89. DOI: 10.1002/pros.10192. View

11.

Ogawa Y, Yamazaki K, Kuwana M, Mashima Y, Nakamura Y, Ishida S . A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD. Invest Ophthalmol Vis Sci. 2001; 42(1):111-9. View

12.

Obata H . Anatomy and histopathology of the human lacrimal gland. Cornea. 2006; 25(10 Suppl 1):S82-9. DOI: 10.1097/01.ico.0000247220.18295.d3. View

13.

Rios J, Horikawa Y, Chen L, Kublin C, Hodges R, Dartt D . Age-dependent alterations in mouse exorbital lacrimal gland structure, innervation and secretory response. Exp Eye Res. 2005; 80(4):477-91. PMC: 3243076. DOI: 10.1016/j.exer.2004.10.012. View

14.

Mircheff A, Gierow J, Lee L, Lambert R, Akashi R, Hofman F . Class II antigen expression by lacrimal epithelial cells. An updated working hypothesis for antigen presentation by epithelial cells. Invest Ophthalmol Vis Sci. 1991; 32(8):2302-10. View

15.

Jabs D, Wingard J, Green W, Farmer E, Vogelsang G, Saral R . The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease. Arch Ophthalmol. 1989; 107(9):1343-8. DOI: 10.1001/archopht.1989.01070020413046. View

16.

Pflugfelder S, Wilhelmus K, Osato M, Matoba A, Font R . The autoimmune nature of aqueous tear deficiency. Ophthalmology. 1986; 93(12):1513-7. DOI: 10.1016/s0161-6420(86)33528-0. View

17.

Nguyen C, Peck A . Unraveling the pathophysiology of Sjogren syndrome-associated dry eye disease. Ocul Surf. 2009; 7(1):11-27. PMC: 2861866. DOI: 10.1016/s1542-0124(12)70289-6. View

18.

Jonsson M, Delaleu N, Brokstad K, Berggreen E, Skarstein K . Impaired salivary gland function in NOD mice: association with changes in cytokine profile but not with histopathologic changes in the salivary gland. Arthritis Rheum. 2006; 54(7):2300-5. DOI: 10.1002/art.21945. View

19.

Draper C, Singh J, Adeghate E . Effects of age on morphology, protein synthesis and secretagogue-evoked secretory responses in the rat lacrimal gland. Mol Cell Biochem. 2003; 248(1-2):7-16. DOI: 10.1023/a:1024159529257. View

20.

Zhu Z, Stevenson D, Schechter J, Mircheff A, Atkinson R, Trousdale M . Lacrimal histopathology and ocular surface disease in a rabbit model of autoimmune dacryoadenitis. Cornea. 2002; 22(1):25-32. DOI: 10.1097/00003226-200301000-00007. View