Comparison of microglia and infiltrating CD11c+ cells as antigen presenting cells for T cell proliferation and cytokine response

Background: Tissue-resident antigen-presenting cells (APC) exert a major influence on the local immune environment. Microglia are resident myeloid cells in the central nervous system (CNS), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. Dendritic cells (DC) and macrophages infiltrate the CNS during experimental autoimmune encephalomyelitis (EAE). Microglia are not considered to be as effective APC as DC or macrophages. Methods: In this work we compared the antigen presenting capacity of CD11c(+) and CD11c(-) microglia subsets with infiltrating CD11c(+) APC, which include DC. The microglial subpopulations (CD11c(-)CD45(dim)CD11b(+) and CD11c(+) CD45(dim) CD11b(+)) as well as infiltrating CD11c(+)CD45(high) cells were sorted from CNS of C57BL/6 mice with EAE. Sorted cells were characterised by flow cytometry for surface phenotype and by quantitative real-time PCR for cytokine expression. They were co-cultured with primed T cells to measure induction of T cell proliferation and cytokine response. Results: The number of CD11c(+) microglia cells increased dramatically in EAE. They expressed equivalent levels of major histocompatibility complex and co-stimulatory ligands CD80 and CD86 as those expressed by CD11c(+) cells infiltrating from blood. CD11c(+) microglia differed significantly from blood-derived CD11c(+) cells in their cytokine profile, expressing no detectable IL-6, IL-12 or IL-23, and low levels of IL-1 beta. By contrast, CD11c(-) microglia expressed low but detectable levels of all these cytokines. Transforming growth factor beta expression was similar in all three populations. Although CNS-resident and blood-derived CD11c(+) cells showed equivalent ability to induce proliferation of myelin oligodendrocyte glycoprotein-immunised CD4(+) T cells, CD11c(+) microglia induced lower levels of T helper (Th)1 and Th17 cytokines, and did not induce Th2 cytokines. Conclusions: Our findings show distinct subtypes of APC in the inflamed CNS, with a hierarchy of functional competence for induction of CD4(+) T cell responses.