Proportion of IL-17A Producing CD4+ Cells Increases in Response to Alloreactivity as Part of a Network Involving Memory and Regulatory Cells Post HSCT.

Abstract 1160

Poster Board I-182

Acute GvHD is a major factor affecting the outcome of hematopoietic stem cell transplantation (HSCT). In this study the focus was on the presence of IL-17-producing lymphocytes in patients post-HSCT with respect to FoxP3-positive lymphocytes and those with IFNgamma generation potential.

The cytoplasmic expressions of IL-17, FoxP3, and IFN-gamma were studied in stimulated PBMCs (brefeldin A, Ionomycin, and PMA) of alloHSCT patients (43 patients, median age: 45 yrs, range; 1.0-64 yrs, with 41 hematological malignancies and 2 SCID).The cells were labeled with CD4, IL-17A, IFN-gamma, and FoxP3 MoAbs and analyzed in the CD4+ lymphocyte subpopulation. Twenty patients received MUD and 23 SIB transplants. Twenty developed aGvHD, among them 7 patients with aGvHD seen at a later stage after hematological reconstitution and 4 patients with recurrent clinical manifestation of aGvHD.

It was found that: (1) the percentage of IL-17-producing CD4+ lymphocytes was higher in patients without aGvHD at the beginning of hematological reconstitution than in healthy controls (0.65±0.11% vs. 0.19±0.06%, p=0.02), (2) aGvHD cases with disease onset at the time of hematological reconstitution had lower proportions of IL-17A-producing CD4+ lymphocytes than those without aGvHD at a similar time after HSCT (0.31±0.1% vs. 0.65±0.11%, p=0.04), (3) when individual patients were followed it became apparent that the proportion of IL-17A-producing CD4+ lymphocytes, increased one week prior to aGvHD compared with the preceding observation (1.16±0.43% vs. 0.77±0.33%) and then a significant decrease was seen when symptoms became apparent (1.16±0.43% vs. 0.36±0.16%, p=0.017, Wilcoxon Test), (4) a high degree of correlation was found between the percentages of CD4+IL-17A+ and IFNgamma+CD4+ lymphocytes in blood at the time of hematological recovery (r=0.55, p=0.007), (5) patients with a higher percentage of IL-17A-producing cells in the CD4+ cell population more frequently had a higher proportion of FoxP3 in CD4+ cells (chi2=5.67, p=0.017), (6) the percentage of IFNgamma-producing CD4+ cells correlated with the proportion of FoxP3+ cells in the CD4+ cell population (r=0.48, p=0.02), and (7) the percentage of IL-17A-generating CD4+ cells rather inversely correlated with the proportion of CCR7+ lymphocytes in the blood of patients at the beginning of hematological recovery (r=-0.35, p=0.10).