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.