The frequency of CMV-specific CD4⁺ T cells is increased in patients with a history of treatment. CMV-specific CD4⁺ T cells were measured in CMV-seropositive patients and expressed (A) as a percentage of the CD4⁺ T-cell pool or (B) as an absolute number. The mean percentage of CMV-specific CD4⁺ T cells was 17%, 16%, and 5.8% for IFNγ, TNFα, and IL-2 responses, respectively, in patients with a history of treatment compared with 8.06%, 7.08%, and 1.41%, respectively, in untreated patients (P = .017, P = .015, and P = .019). The mean number of CMV-specific CD4⁺ T cells in CMV-seropositive treated patients was 138 300/mL, 115 800/mL, and 39 200/mL for IFNγ, TNFα, and IL-2 responses, respectively, compared with 55 900/mL, 42 400/mL, and 6270/mL in untreated patients (P = .047, P = .045, and P = .015, respectively). (C) A significant difference was observed in the frequency and number of IFNγ-positive CMV-specific CD4⁺ T cells between untreated CMV-seropositive patients and the CMV-seropositive control group (mean 8.06% of CD4⁺ T cells compared with 4.3%, P = .03, and 55 900/mL compared with 24 100/mL, P = .04; n = 35).