A class II-restricted chlamydia-specific CD8ɣ13 T cell clone protects the genital tract during Chlamydia muridarum infection

The T cell response to Chlamydia genital tract infections in humans and mice is unusual in that the majority of antigen-specific CD8 T cells are not restricted by HLA/MHC class I and therefore have been referred to as “unrestricted” or “atypical”.   We previously reported that a subset of unrestricted murine Chlamydia-specific CD8 T cells had an unusual cytokine polarization pattern that included IFN-ɣ and IL-13.  For this report, we investigated the transcriptome of Chlamydia-specific CD8ɣ13 T cells, comparing them to Chlamydia-specific multifunctional Tc1 clones using gene expression micro array analysis.  The molecular study revealed that CD8ɣ13 polarization included IL-5 in addition to IFN-γ and IL-13.  Adoptive transfer studies were performed with Tc1 clone and CD8ɣ13 T cell clones to determine whether either influenced bacterial clearance or immunopathology during Chlamydia muridarum (Cm) genital tract infections.  To our surprise, an adoptively transferred CD8ɣ13 T cell clone was remarkably proficient at preventing chlamydia immunopathology while the multifunctional Tc1 clone did not enhance clearance or significantly protect from immunopathology.  Mapping studies with MHC class I- and class II-deficient splenocytes showed our previously published Chlamydia-specific CD8 T cell clones are MHC class II-restricted.   MHC class II-restricted CD8 T cells may play important roles in protection from intracellular pathogens that limit class I antigen presentation or deplete the CD4 T cell compartment. CD8γ13 T cell clones were compared to Tc1 T cell clones and an alloreactive conventional CD8 T cell clone in dormant resting state and after activation with immobilized anti-CD3 antibody for 14 hours.