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Published on: November 17, 2014
Cell populations and adhesion molecules expression in conjunctiva before and after bone marrow transplantation
B Rojas1, R Cuhna, P Zafirakis
1Hilles Immunology Laboratory, Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114, USA. brojas@med.ucm.es
Insights
Bone marrow transplantation (BMT) alters conjunctival immune cells and adhesion molecules. Allogeneic BMT with chronic graft-versus-host disease (GVHD) significantly increases T cells and macrophages, particularly in patients with dry eye and keratoconjunctivitis sicca (KCS).
Area of Science:
- Ophthalmology
- Immunology
- Hematology
Background:
- Bone marrow transplantation (BMT) can lead to ocular complications, including dry eye.
- Understanding conjunctival immune changes post-BMT is crucial for managing ocular surface disease.
Purpose of the Study:
- To analyze conjunctival cellular infiltrate and adhesion molecule expression before and after autologous and allogeneic BMT.
- To investigate the relationship between these changes and the presence of dry eye, particularly keratoconjunctivitis sicca (KCS).
Main Methods:
- Immunohistochemistry was performed on conjunctival biopsies from patients before and after BMT.
- Monoclonal antibodies were used to identify T-lymphocytes (CD3, CD4, CD8), macrophages (CD14), and various adhesion molecules (ICAM-1, VCAM-1, LFA-1, VLA-4).
- Patients were assessed for graft-versus-host disease (GVHD) and dry eye symptoms.
Main Results:
- Autologous BMT increased epithelial T-lymphocytes and stromal CD4+/CD14+ cells, along with VLA-4 expression.
- Allogeneic BMT (with chronic GVHD) significantly increased epithelial and stromal T-lymphocytes and CD14+ cells, plus stromal VLA-4 and LFA-1 expression.
- In allogeneic recipients, increased CD14+ cells in the conjunctiva correlated with dry eye and KCS, and higher CD4/CD8 ratios were observed in KCS patients.
Conclusions:
- Autologous BMT induces a subclinical cell-mediated immune response in the conjunctiva.
- Conjunctivitis associated with chronic GVHD is a complex immune process involving T-cells and macrophages.
- Conjunctival immune alterations post-BMT, especially in allogeneic cases, are linked to dry eye development and severity.
Abstract:
We were interested to analyse the composition of the cellular infiltrate and adhesion molecules expression in the conjunctiva before and at least one hundred days after autologous and allogenic bone marrow transplantation (BMT) and its relation with the presence of dry eye. We used immunohistochemistry on cryopreserved human conjunctiva with monoclonal antibodies to T-lymphocytes (CD3, CD4 and CD8), B-lymphocytes (CD19), macrophages (CD14), natural killer cells (NK, CD57), intercellular adhesion molecule 1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), lymphocyte function associated antigen-1 (LFA-1), very late antigen-4 (VLA-4), interleukin 2 receptor (IL2r, CD25) and HLA-DR. Our autologous recipients had no graft-versus-host disease (GVHD) but allogenic patients had chronic GVHD. After autologous BMT the conjunctiva had significantly more: (1) T lymphocytes (CD3+, CD4+, CD8+) in the epithelium; (2) CD4+ and CD14+ cells in the stroma; and (3) VLA-4 expression in the stroma than before BMT. After allogenic BMT, the conjunctiva exhibited a significant increase of: (1) CD3+ and CD14+ cells in the epithelium; (2) T lymphocytes (CD3+, CD4+, CD8+) and CD14+ cells in the stroma; and (3) VLA-4 and LFA-1 expression in the stroma than before BMT. After the engraftment, the comparison between autologous and allogenic recipients revealed that: (1) there were no significant differences in adhesion molecule expression; (2) the epithelium of autologous recipients had significantly more CD3+ cells; and (3) the stroma of allogenic patients had significantly more CD3+ and CD8+ cells. Among allogenic recipients, CD14+ cells were significantly increased both in the epithelium and in the stroma of patients with signs or symptoms of dry eye in comparison with patients without ocular involvement. Additionally, those having keratoconjunctivitis sicca (KCS) had CD4/CD8 ratios significantly higher than those without KCS. In conclusion, in the conjunctiva after autologous BMT a subclinical cell mediated immune reaction seems to take place. The conjunctivitis of chronic GVHD is complex, with T cells and macrophages dramatically contributing to the process.
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