Detailed immunophenotype of CD8 + memory cytotoxic T-lymphocytes (CTL) against HIV-1 with respect to expression of CD45RA/RO, CD62L and CD28 antigens

We have previously reported that circulating effector cytotoxic CD8 + T-lymphocytes (CTLs) against HIV-1 express CD38 and HLA-DR activation antigens. In this study, we performed two series of FACS sorts to phenotype and characterize precursors of CTL effectors. First we looked at memory CTL activity against HIV-1 stimulated by antigen as well as CTL activity stimulated by CD3 mAb with regard to whether the precursors expressed CD45RA and/or CD62L. We found that the precursor cells that could be stimulated with antigen to become effectors within 7 days predominated in the CD45RA − CD62L − subset. However, in donors with low levels of CD8 + T-cell activation as measured by CD38 antigen expression, memory cells could also be found in the CD45RA + CD62L + subset. Our data indicate that reversion of memory cells to the CD45RA + CD62L + phenotype can occur in humans, especially in donors with low levels of virus replication and minimal CD8 + T-cell activation. Next, we looked at CD28 expression with regard to antigen specific memory cells and again found that the level of virus replication and CD8 + T-cell activation influenced the subset that contained the memory cells. In donors with high levels of virus replication, our results indicated that CTL were being actively recruited from both CD28 + and CD28 − subsets, while in donors with undetectable levels of viral replication, the memory cells were entirely in the CD28 − compartment.