Do intrasynovial T lymphocytes facilitate disease progression in patients with rheumatoid arthritis?

Rheumatoid arthritis (RA) is attributed to inflammation and infiltration of immune cells into the inflamed joints. In the synovial fluid (SF), accumulated neutrophils can transdifferentiate into neutrophil-dendritic cell hybrids (N-DCs) and acquire antigen presenting properties. This study aimed to establish the crosstalk, if any, between N-DCs and T lymphocytes in the SF as also assess their potential role in disease sustenance.

In the SF of patients with RA (n=15), the frequency and activation status of CD4+ and CD8+ T lymphocyte subsets (i.e. memory, naive, central memory or CM, and effector memory or EM) was examined by immunophenotyping (CD4, CD8, CD45RO, CD45RA, CD62L, CD197 and CD69), along with their generation of reactive oxygen species, cytotoxic potential (Granzyme-B), status of pro-inflammatory receptor (CXCR3) and co-stimulation (CD28). Subsequently, the frequency and characterisation of doublets was done by flow cytometry.

In the SF, there was an enhanced proportion of activated CD4+ and CD8+ EM T lymphocytes, that positively correlated with Disease Activity Score DAS28. These EM T lymphocytes demonstrated an enhanced generation of ROS, enhanced cytotoxic potential and were CXCR3+/CD28+. Furthermore, doublets were identified between N-DCs and activated CD4+ EM T lymphocytes, and ex-vivo studies confirmed that their inflammatory milieu facilitated transdifferentiation, activation of T lymphocytes and doublet formation.

In the SF of patients with RA, disease progression was facilitated by formation of doublets between N-DCs and activated effector memory CD4+ T lymphocytes.