Experimental Graft Versus Host Disease in the (BN × LEW) Fl Rat Hybrid as a Model for Autoimmune Disease. Study of Early Adenitis in Lacrimal and Salivary Glands

Abstract

We analysed inflammatory changes at selected time intervals, of salivary and lacrimal glands in the developing immunostimulatory [BN → (BN × LEW)Fl] model of graft-versus-host (GVH) reaction. A focal mononuclear adenitis in lacrimal and salivary glands developed at day 7 and increased clearly in “onset”-rats. Inflammatory responses in submandibular and parotid glands were less consistent and weaker than in lacrimal glands. There was no significant focus score difference between males and females.

The lacrimal infiltrates were characterised immunohistochemically with monoclonal antibodies. Our findings indicate that CD4⁺ cells of donor origin dominated infiltrates, whereas a moderate number of B cells appeared only in large (late) foci. At stages corresponding to the onset of GVH disease (GVHD) in skin/labial mucosa, numerous CD8⁺ lymphocytes and NK cells were found in lacrimal glands, adjacent to ductal/vascular plexa, sometimes forming small foci and with evidence of epithelial damage.

We conclude that GVHD-associated T cell migration into rat exocrine glands occurs as a result of the semi-alloantigen-activated phenotype properties of the T cells. This activation occurs initially in lymphoid tissue and migration into glands is secondary to this and unrelated to antigen specificity. We also found evidence of amplification and tissue damage, interpreted as due to local reactivation of the T cells.

Key Words:

• graft versus host
• BN
• rat
• exocrine glands
• T-cells