Do GM-CSF producing CD4 T cells (Th-GM cells) play a role in Experimental Autoimmune Prostatitis?

GODOY, GLORIA J.; RIVERO, VIRGINIA E.; SALAZAR, FLORENCIA C.; MOTRICH, RUBEN D.

Mar del Plata

Congreso; LXIV Reunión Anual de SAI, LXI Reunión Anual de la SAIC, XLVIII Reunión Anual de la SAFE, VII Reunión Anual de la NANOMEDAR, V Congreso Nacional de la AACyTAL.; 2016

Chronic Pelvic Pain Syndrome (CPPS) is the most prevalent urologic disease. Its aetiology remains elusive and autoimmunity has been proposed as a cause. Experimental Autoimmune Prostatitis (EAP) models have been largely used for the study of CPPS. To date, they have revealed a major role of Th1 lymphocytes in the development of disease. Recently, GM-CSF produced by CD4 T helper cells (Th-GM cells) have been described and identified to serve a nonredundant function in the initiation of autoimmunity.Here, we studied the overall immune response and disease development in our model of EAP in NOD and C57BL/6 mice, with special focus on the induction of Th-GM cells. Either NOD or C57BL/6 mice were immunized with prostate antigens (PA) or saline (C) plus complete Freund?s adjuvants on days 0 and 15. Animals were euthanized on day 24 and the induction of PA-specific immune response (Th1 and Th-GM cells), prostate histopathology and tissue infiltrating leukocytes were analyzed. Significantly increased levels of GM-CSF+RORgt+ and RORgt+IL22+ CD4 T cells were detected in prostate draining lymph node cells from PA-immunized NOD mice when compared to controls (p>0.05). However, those levels were lower than the markedly higher levels of IFNg+ CD4 T cells detected, revealing the induction of a prominent Th1 immune response. These peripheral immune responses resulted in prostate tissue inflammatory lesions (hemorrhage, edema, epithelial cell desquamation) and periglandular leukocyte infiltration. Infiltrates were mainly composed of CD4 T cells, macrophages and Gr1+ cells. Similar results were found when analyzing C57BL/6 mice. As expected, control animals did not develop either PA-specific immune responses or prostate inflammation.Our results demonstrate that Th-GM cells are induced upon PA-immunization in EAP. However, Th1 cells are still the most prominently elicited immune response after immunization suggesting that Th-GM cells are playing a secondary/redundant role in EAP.