Functional response to hCMV in patients with monoclonal CD4⁺ T-LGL vs other T-cell chronic lymphoproliferative disorders (T-CLPDs). (A) Most patients with monoclonal TCR-βα⁺/CD4⁺ T-LGL lymphocytosis (n = 11 of 12; 92%) showed activated hCMV-specific TNF-α⁺ clonal T cells in response to the viral lysate, whereas this response was found at much lower frequencies (P < .001) among other T-CLPDs analyzed (n = 2 of 18; 11%). The hCMV-specific response was also reflected by increased secretion of both IFN-γ (P < .001) and TNF-α (P < .01) into the culture supernatant in response to hCMV, but not hEBV (B), as well as by an increased expression of both the CD69 and CD25 activation-associated markers (P < .05) (C). In turn, extremely high levels of soluble IFN-γ were found after stimulation with the MQLIPDDYSNTHSTRYVTVK hCMV peptide, complementary of the HLA-DRB1*0701 allele, in patients with monoclonal TCRVβ13.1⁺/CD4⁺ T-LGL lymphocytosis compared with other T-CLPD cases carrying this HLA haplotype (P < .05) (D). Boxes in panels B to D extend from the 25th to the 75th percentiles; the line in the middle and vertical lines correspond to the median value and both the 10th and 90th percentiles, respectively.