Cytotoxic T Lymphocyte Precursor Frequency Does Not Correlate With Either the Incidence or Severity of Graft-Versus-Host Disease After Matched Unrelated Donor Bone Marrow Transplantation1

Generation of leukemia-reactive cytotoxic T lymphocytes from HLA-identical donors of patients with chronic myeloid leukemia using modifications of a limiting dilution assay

“…19,27,28 However, some patients with high frequencies developed minimal acute GVHD, whereas other patients with low frequencies had moderate to severe GVHD. 29 A possible explanation for these differences may be the restricted tissue distribution of some minor histocompatibility (mH) antigens. 30 Antigens capable of initiating acute GVHD in a particular organ may not be expressed by the antigen-presenting cells used as stimulator cells in the LDA and hence will not be detected by the assay.…”

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

“…Historically, the CTLp assay was used to quantitate the precursor frequency of allospecific T cells that could potentially expand and induce an alloresponse. The value of this assay has been controversial with opposing perspectives on the predictive power of the assay and clinical outcome (18)(19)(20)(21)(22)(23)(24)(25). Therefore we assessed the correlation between CTLp (LDA-based) and the proportion of T CD8+ cells with allospecificity after 13 days culture in vitro and measured in the MLR-ICS assay.…”

“…Quantitation of allospecific T-cell precursors, using limiting dilution based assays (LDA; cytotoxic T lymphocyte precursor [CTLp] and helper T lymphocyte precursor) (8,9), have all been used to assess the in vitro allogeneic potential of HLA mismatches (10)(11)(12)(13)(14)(15)(16)(17). However, the correlation between the quantitation of allospecific T-cell precursor frequencies and incidences of graft rejection or GvHD has been disappointing and laboratory-dependent (18)(19)(20)(21)(22)(23)(24)(25). Indeed, limitations of LDA based applications have been highlighted through enumeration of antigen-specific T cells in both human (26)(27)(28) and murine models (29).…”

Cytotoxic T lymphocyte precursor frequency as a predictor of acute graft-versus-host disease in bone marrow transplantation from HLA-identical siblings

“…High frequencies of HTL-p have been shown to correlate with an increased risk for aGVHD development in unrelated donor 13 and HLA-identical sibling 5,6,23,30 BMT, although this can not always be confirmed. 15,31 Several studies 7,32,33 have demonstrated a correlation between high CTL-p frequencies and a significantly higher incidence of severe aGVHD and death in unrelated donor BMT, whereas in other reports 34,35 these results have not as yet been confirmed. In HLA-identical sibling BMT, the CTL-p assay did not appear to be sensitive enough to provide similar predictive information.…”