Cytokine Gene Expression in Peripheral Blood Mononuclear Cells and Alloreactivity in Hematopoietic Cell Transplantation with Nonmyeloablative Conditioning

Cytokine gene expression in an HLA-mismatched mixed lymphocyte culture: longitudinal analysis of the relative mRNA level in 5 × 10⁴ MNCs stimulated with 5 × 10⁴ irradiated HLA-mismatched MNCs over 10 days in 2 individuals. Mean and range (error bars) are shown.

Cytokine gene expression in recipient and donor mononuclear cells (MNCs). The relative mRNA level is shown of IL-2 (a), IL-4 (b), TNF-α (c), IL-10 (d), TGF-β (e), and IL-18 (f) in cultures of responder MNCs, obtained before transplantation from 21 recipients (R) and 21 donors (D). The responder MNCs were unstimulated or stimulated with irradiated HLA-identical MNCs (xD) and (xR), irradiated HLA-mismatched third-party MNCs (xTP), or PHA. The median and 25th and 75th percentiles (boxes) and the range (whiskers) are shown. The results were compared within the recipient and donor cohorts with the Friedman test and between the recipients and donors with the Kruskal-Wallis test. The Dunn multiple comparison correction was used for the posttests: ***P < .001; **P < .01; *P < .05.

Cytokine gene expression after hematopoietic cell transplantation. The relative mRNA level is shown of TNF-α, IL-18, and IL-2 (a) and of TGF-β, IL-10, and IL-4 (b) during the first year after transplantation in cultures that were either unstimulated or stimulated with irradiated recipient MNC (xR) or irradiated donor MNCs (xD).

Acute GVHD, cytokine gene expression, and composition of the mononuclear cells. The relative mRNA level is shown of TGF-β and IL-10 during the first year after transplantation in cultures from patients with acute GVHD grades 0 and I or grades II to IV. The results are shown for cultures that were unstimulated (a) or stimulated with irradiated HLA-mismatched third-party MNCs (b), irradiated recipient MNCs (c), or irradiated donor MNCs (d). The fractions of monocytes (e) and of CD4⁺ and CD8⁺ T cells (f) in the responder cells of patients with acute GVHD grades 0 and I or grades II to IV are shown. xR indicates irradiated recipient MNC; xTP, irradiated HLA-mismatched third-party MNCs; xD, irradiated donor MNCs.

Correlation of the pretransplantation IL-10 mRNA level with the level on day +14. The relative pretransplantation IL-10 mRNA level in the unstimulated cultures with cells of recipient origin (a and b) or of donor origin (c and d) was correlated with the relative IL-10 mRNA level in the cultures performed with responder cells obtained on day +14. The cultures on day +14 were stimulated with irradiated recipient MNCs (xR) or with irradiated donor MNCs (xD). The Spearman r and the corresponding P value are shown.

Pretransplantation IL-10 mRNA levels, relapse, and acute GVHD. The relative levels of IL-10 mRNA in unstimulated recipient (R) or donor (D) MNCs obtained before transplantation were compared on the basis of the occurrence of acute GVHD grades 0 and I or II to IV (a) and relapse/progression (b). The P values of the Mann-Whitney tests are shown.