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.