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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.

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