Time-dependent serial changes of antigen-presenting cell subsets are distinct between the corneal sterile inflammation and allosensitization

Abstract

Purpose : The kinetics of antigen-presenting cells (APCs) vary depending on their resident tissues and the manner of sensitization. We investigated the long-term kinetics of APCs in Balb/c mouse models of corneal quiescent or potent sterile inflammation and allosensitization using corneal partial trephination, syngeneic, and allogeneic corneal transplantation.

Methods : Balb/c mice were assigned into 4 groups: control, corneal partial trephination (PT), 2.5 mm-to-2.0 mm syngeneic (Syn) and C57BL/6 to Balb/c allogeneic corneal transplantation (Allo). The serial changes in CD11b^-CD11c⁺MHCII^hi, CD11b⁺CD11c⁺MHCII^hi, and CD11b⁺CD11c^-MHCII^hi, and CD69^hi or interferon gamma (IFNγ)^hi effector T cell subsets were evaluated in the ocular surface, draining lymph nodes (dLNs), and spleen for over 4 weeks.

Results : In PT, CD11b^-CD11c⁺MHCII^hi and CD11b⁺CD11c⁺MHCII^hi subsets increased until 4 weeks with increases in ocular IFNγ^hi T cells. In Syn, ocular CD11b⁺CD11c⁺MHCII^hi and CD11b⁺CD11c^-MHCII^hi cells increased until 4 weeks with an increase in ocular CD69^hi T cells. However, in Allo, the ocular and lymph nodal CD11b⁺CD11c⁺MHCII^hi and CD11b⁺CD11c^-MHCII^hi cells and ocular CD11b⁺CD11c^-MHCII^hi cells significantly increased until 4 weeks and primed both the ocular and lymph nodal IFNγ^hi and CD69^hi T cell subsets. Ocular CD11b⁺CD11c⁺MHCII^hi subset appears to be a major population that becomes mature MHCII^hi APCs, regardless of the inflammation type.

Conclusions : This indicates that allosensitization activates the corneal CD11b^-CD11c⁺MHCII^hi, CD11b⁺CD11c⁺MHCII^hi and CD11b⁺CD11c^-MHCII^hi cells leading nodal maturation of CD11b^-CD11c⁺MHCII^hi and CD11b⁺CD11c⁺MHCII^hi subsets to interact with nodal T cells, whereas sterile inflammation seems to induce ocular T cell interaction independently of the nodal activation of APCs.

This is a 2021 ARVO Annual Meeting abstract.

 

The hypothetical illustration shows how the distinct antigen-presenting cell subsets interact with T cells depending on the type of corneal immune response in mice.