Combining cellular immunology with RNAseq to identify novel chlamydia T cell subset signatures

Chlamydia trachomatis serovars A-L cause important diseases of the eyes and reproductive tract by infecting epithelium lining those organs. A major hurdle for vaccine trials is finding a surrogate biomarker for protective immunity. Investigational data argues for T cell biomarker(s) reflecting mucosal adaption, cytokine polarization, B cell help, antibacterial effector mechanisms, or some combination thereof. A human investigation and two mouse studies link IL-13 to protection from infection/immunopathology. We performed RNAseq on T cells resident in spleens and genital tracts (gt) of naturally immune mice. CD4 signatures were consistent with helper function that differed by site including a gt specific Fgl2 signal. The gt CD8 signature featured IL-10 and promotion of healing/scarring with a unique transcription of granzyme A. The RNAseq data was used to refine previously published CD4?13 and CD8?13 transcriptomes derived from protective T cell clones, potentially identifying practicable T cell subset signatures for assessing chlamydia vaccine candidates. Overall design: T cell profiles of spleen and genital tracts from mice after seconday infection of Chlamydia muridarum