HHV8-specific T-cell profiling in 2 PT-KS patients who achieved remission after switch to sirolimus. IFNγ-enzyme–linked immunosorbent spot assay (IFNγ-ELISPOT; top panels) and cytokine secretion assay (CSA; bottom panels) were used to perform HHV8-specific immunologic monitoring in 2 renal recipients (patient A, left panels; patient B, right panels), who developed skin PT-KS after 9 and 18 months from transplantation, respectively. Both lytic (orfK8.1) and latent (orf73/LANA) HHV8-derived antigens were used as specific T-cell stimulations in both assays. After switching from tacrolimus- to sirolimus-based immunosuppressive regimens, both patients rapidly achieved complete PT-KS regressions and concurrently showed the recovery of HHV8-specific cytotoxic T cells. Such responses, which were absent at PT-KS diagnosis, were readily detectable during all post-remission follow-up, as demonstrated by IFNγ-ELISPOT long-term immunologic monitoring. Furthermore, in both cases, we applied CSA assays to perform a phenotypic and functional characterization of HHV8-specific T cells, either at the time of PT-KS onset (or before, in patient A) or after remission. Here we have also shown that frequencies of different HHV8-specific T-cell subsets, as defined by surface markers (CD4⁺ and CD8⁺) and cytokine productions (IFNγ, IL-17, IL-4, IL-10, and IL-2), may also well correlate with the disease course, possibly revealing a “nonprotective” Th2 prevalence at time of PT-KS diagnosis and a “protective” Th1 prevalence after remission. HHV8-specific T-cell subsets are expressed as percentages of total CD4⁺ or total CD8⁺ T cells. Nonspecific memory T-cell profiling data are also reported over the related CSA assays. PDN indicates prednisone; SRL, sirolimus; IFNγ-SFCs, interferon-γ–producing spot-forming cells; PHA, phytohemagglutinin; CEF, CMV, EBV, influenza virus-derived antigens; CM, central memory; EM, effector memory; and EMRA, CD45RA⁺ effector memory.