*Purpose: Group 2 innate lymphoid cells (ILC2s) have been shown to play key roles in manipulating adaptive immunity. They regulate CD4⁺ T cell biology not only through the production of cytokines, but also MHCII dependent crosstalk that reshapes intestinal microbiota and promotes parasites expulsion. Whether ILC2s are important in the alloimmune response is unknown.

*Methods: BALB/c mice hearts were transplanted into abdominal cavity of C57BL/6 recipients . Recipients were sacrificed and grafts cells were obtained by collagenase digestion. ILC2s were defined as linage^–CD45⁺CD127⁺Gata3⁺ (Linage dump channel includes Ter119, CD3, CD19, CD11b and CD11c) and their phenotypes were analyzed by flow cytometry. Donor MHC I (H-2kd) and recipient MHC I (H-2Kb) were used to identify cell origin.

*Results: ILC2s were the predominant ILC population both in naïve and transplanted hearts. Five days after transplant, most of the heart graft ILC2s (87.55% ± 8.73%) were from recipient. Graft ILC2s expressed same level of ST2 but upregulated CD25 compared to naïve BALB/c hearts. Following allografts implantation, recipient derived ILC2s upregulated MHC II (15.92% ± 4.67%) without cross-dressed donor MHC II (I-Ad). In contrast, donor derived ILC2s and naïve BALB/c hearts ILC2s don’t express MHC II molecules. Moreover, expression of CD80 and CD86 from donor or recipient derived ILC2s were undetectable in explanted heart grafts.

*Conclusions: Recipient ILC2s infiltrate heart allografts following transplant, likely through CD25 dependent proliferation. Graft ILC2s upregulate MHCII without a corresponding upregulation of co-stimulatory ligands. Our findings suggest ILC2s have could have a potential role in inducing MHC II dependent CD4⁺ T cell anergy thereby diminishing alloimmune responses.

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