Immune repertoire profiling uncovers pervasive T-cell clonal expansions in benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is the nodular proliferation within the prostatic transition zone leading to urinary voiding problems often refractory to therapy. Lymphocytic infiltrates in BPH have implicated inflammatory processes, though the particulars remain unknown. Here, we investigated lymphocytic infiltrates by B-cell receptor (BCR) and T-cell receptor (TCR) repertoire profiling of BPH nodules. While BCR repertoires exhibited high diversity, TCR repertoires showed striking oligoclonality pervasive among BPH stromal and stromal-epithelial mixed nodules, with several T-cell clonotypes reaching 10-30% of all T cells. The oligoclonal T cells were CD8+ (cytotoxic T cells), and classic cytotoxic T-cell cytokines interferon-gamma and tumor necrosis factor stimulated proliferation of quiescent BPH fibroblasts. Some oligoclonal TCR complementarity-determining regions (CDR3) were predicted to recognize epitopes of common viruses (cytomegalovirus and Epstein-Barr virus), but most had no known antigen matches. Lastly, BPH nodules expressed chemokine CXCL13, while many oligoclonal T cells expressed its receptor CXCR5, implicating CXCL13-CXCR5 signaling in lymphocyte recruitment. Our findings provide to our knowledge the first demonstration of specific adaptive immune (T-cell) responses in BPH. While further studies should clarify the T-cell subsets, their spatiotemporal distributions, and the inciting antigens, our findings support exploration of immune modulating therapies in the prevention or treatment of BPH.