Tissue-resident memory T (T) cells are well known to play critical roles in peripheral tissues during virus infection and tumor immunology. Our previous studies indicated that CD69CD4 and CD69CD8 T cells in tuberculous pleural effusion (TPE) were antigen-specific memory T cells. However, the phenotypical and functional characteristics of CD8 T cells in tuberculosis remain unknown. We found that CD103CD8 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, CD103CD69 and CD103CD69CD8 T cells expressed higher levels of CD45RO than CD103CD69CD8 T cells did; CD103CD69CD8 T cells highly expressed CD27, CD127, and CD62L and some chemokine receptors. We further compared the functional differences among the four distinct CD45ROCD8 T subsets identified by CD103 and CD69 expression. In consist with our published results, CD69CD8 T cells, but not CD103CD8, produced high levels of IFN- after treatment with BCG in the presence of BFA. Nevertheless, CD103CD69 and CD103CD69 memory CD8 T cells expressed higher levels of Granzyme B, while CD103CD69 memory CD8 T cells were characterized as a possibly immunosuppressive subset by highly expressing CTLA-4, CD25, and FoxP3. Furthermore, TGF- extremely increased CD103 expression but not CD69 . Together, CD103CD8 T cells form the predominant subset of CD103 lymphocytes in TPE; CD103 and CD69 expression defines distinct CD8 T-like subsets exhibiting phenotypical and functional heterogeneity. Our findings provide an important theoretical basis to optimize and evaluate new tuberculosis vaccines.