Internutionul Journul of Infectious Diseases (2006) 10($1) Abstracts viral load (<16,000 copies/10s); Group 3 (n--4) stable, high viral load (>16,000 copiesl10S); Group 4 (n--4) history of PTLD, no detectable/low viral load.Flow cytometric analysis with HLA-A2 or -B8 tetramer (TMR) probes was performed on peripheral blood.The polarization of EBV-specific CD8+T cells (IFN-glIL-511L-10) was assessed by ELISPOT or ELISA.Results: Overall, the "lytic" specific CD8+T cells were more frequent than the "latent" ones and displayed distinct memory phenotypes (Effector Memory vs Central Memory).In addition, higher EBV loads triggered higher frequencies of TMR+ cells (G2 = G3 ~ G1), while patients with history of PTLD (G4) maintained high TMR+ frequencies.Interestingly, although patients in groups G2, G3 and G4 had high frequencies of "lytic" TMR+ cells (1.3+2% vs 2.3+3.4% vs 1.1-1-0.9%),G2 and G4 exhibited higher frequencies of IFN-y producing cells (30+30 and 32+23 spots/10s), suggesting functional EBV-memory CDS+T cells, while G3 displayed impaired IFN-y (19+31 spots/10s), indicative of functional exhaustion.Although EBV stimulation triggered preponderantly IFN-y, the IFN-y/IL-5 ratio was lower in all patients (2.5:1) as compared to adult controls (5:1) yet another unique feature of immune responses in pediatric patients.CDS+T cells in G3 produced higher levels of IL-10 as compared to other groups.Conclusion: These results demonstrate significant differences in EBV-specific memory CDS+T cells from pediatric HTx patients based on their EBV clinical/viral load status.The functional impairment of CDS+T cells from G3 patients might be either a direct result of chronic EBV challenge, or might be due to biased polarization (intermediate IL-5) or to Treg development (high IL-10).
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Deffernez et al. (2006) studied this question.