B cell presentation of Chlamydia antigen selects out protective CD4ɣ13 T cells; implications for genital tract tissue resident memory lymphocyte clusters

Surveillance and defense of the enormous mucosal interface with the nonsterile world is critical to protecting the host from a wide range of pathogens.  Chlamydia trachomatis (Ct) is an intracellular bacterial pathogen that replicates almost exclusively in the epithelium of the reproductive tract.  The fallopian tubes and vagina seem poorly suited to surveillance and defense as they have limited immune infrastructure positioned near the epithelium.  However, a dynamic process during clearing primary infections leaves behind new immune infrastructure positioned near epithelium.  Memory lymphocyte clusters (MLC) harboring tissue resident memory T cells (TRM) are presumed to play an important role in protection from subsequent infections.  Histologically Chlamydia MLC appear to be based on B cells.  We therefore investigated B cell populations in the murine genital tract post-clearance of C. muridarum infections and the nature of T cells recovered from immune mice using immune B cells as antigen presenting cells (APC).  These studies revealed a plasma B cell population in the genital tract consistent with histopathology seen in mouse and human Chlamydia infections, and discovery of a novel CD4 T cell subset based on production of IFN-ɣ and IL-13.   We discuss these results in the context of Trm and previously published data showing that in humans a peripheral blood mononuclear IL-13 response to elementary bodies (EB) predicts resistance to future infection. Modification of T cell expansion using purified immune B cells as APC rather than published unfractionated immune splenocyte APC; resulting T cell clones from immune mice were analyzed to identify subset-specific differences