Tissue-Resident Memory-Like CD8⁺ T Cells Exhibit Heterogeneous Characteristics in Tuberculous Pleural Effusion

Tissue-resident memory T (T_RM) cells are well known to play critical roles in peripheral tissues during virus infection and tumor immunology. Our previous studies indicated that CD69⁺CD4⁺ and CD69⁺CD8⁺ T cells in tuberculous pleural effusion (TPE) were antigen-specific memory T cells. However, the phenotypical and functional characteristics of CD8⁺ T_RM cells in tuberculosis remain unknown. We found that CD103⁺CD8⁺ T cells were the predominant subset of CD103⁺ lymphocytes in TPE; both CD103 and CD69 expressed on memory CD8⁺ T cells from TPE were significantly increased compared with those from paired peripheral blood. Phenotypically, CD103⁺CD69⁺ and CD103⁺CD69^-CD8⁺ T cells expressed higher levels of CD45RO than CD103^-CD69⁺CD8⁺ T cells did; CD103⁺CD69^-CD8⁺ T cells highly expressed CD27, CD127, and CD62L and some chemokine receptors. We further compared the functional differences among the four distinct CD45RO⁺CD8⁺ T subsets identified by CD103 and CD69 expression. In consist with our published results, CD69⁺CD8⁺ T cells, but not CD103⁺CD8⁺, produced high levels of IFN-γ after treatment with BCG in the presence of BFA. Nevertheless, CD103^-CD69⁺ and CD103⁺CD69⁺ memory CD8⁺ T cells expressed higher levels of Granzyme B, while CD103⁺CD69^- memory CD8⁺ T cells were characterized as a possibly immunosuppressive subset by highly expressing CTLA-4, CD25, and FoxP3. Furthermore, TGF-β extremely increased CD103 expression but not CD69 in vitro. Together, CD103⁺CD8⁺ T cells form the predominant subset of CD103⁺ lymphocytes in TPE; CD103 and CD69 expression defines distinct CD8⁺ T_RM-like subsets exhibiting phenotypical and functional heterogeneity. Our findings provide an important theoretical basis to optimize and evaluate new tuberculosis vaccines.