Frequencies of CD4⁺ and CD8⁺ T cells specific for HCMV proteins IE-1, pp65, gHgLpUL128L (pentamer) and gB in the naïve pool of HCMV-seronegative subjects and in the memory pool of subjects with primary or remote HCMV infection.

<p><b>A, B.</b> Frequencies of protein-specific <b>(A)</b> CD4⁺ and <b>(B)</b> CD8⁺ naïve T cells in 6 HCMV-seronegative subjects are reported. Each symbol represents an individual and horizontal black lines indicate median values. <b>C, D.</b> Frequencies of protein-specific <b>(C)</b> CD4⁺ and <b>(D)</b> CD8⁺ memory T cells in 6 patients with primary HCMV infection tested within one month and 6–12 months after infection onset. <b>E, F.</b> Frequencies of protein-specific <b>(E)</b> CD4⁺ and <b>(F)</b> CD8⁺ memory T cells in 7 subjects with remote HCMV infection are reported.</p

Virological and immunological monitoring of the four groups of solid-organ transplant recipients with or without HCMV infection reactivation.

<p>NA, not applicable.</p>1<p>Follow-up.</p>2<p>Patients of this group showed HCMV specific CD8⁺ only, until about 3 months after transplantation, then developed HCMV-specific CD4⁺ T-cells.</p>3<p>In some cases, clinicians preferred initiating antiviral therapy after reaching 100,000 (instead of 300,000) DNA copies/ml blood due to presence of end-organ disease.</p><p>Virological and immunological monitoring of the four groups of solid-organ transplant recipients with or without HCMV infection reactivation.</p

Comparison of (A) HCMV-specific and (B) total T-cells/µl in group 4 non-protected patients <b><i>vs</i></b><b> groups 1+2+3 protected patients.</b>

<p>While both total and HCMV-specific CD4⁺ T-cells are significantly higher in protected patients, no difference is observed between protected and non-protected patients for both total and specific CD8⁺ T-cells.</p

IL-7R^neg short-term effector _vs IL-7R^pos long-term memory T cells persistance at late time points after primary HCMV infection.

<p>Frequencies of IL-7R^pos T cells in <b>(A-B)</b> total memory and <b>(C-D)</b> HCMV-specific CD4⁺ or CD8⁺ T cells are reported. Data are from HCMV-seronegative subjects (“No infection”, n = 5, only for total memory), patients (both pregnant and non-pregnant) within 1 month (n = 25) or at 6–12 months (n = 18) after primary infection onset, and subjects with remote infection (n = 10). “HCMV-specific” indicates the sum of the single protein-specific T cells. Each symbol represents an individual and column upper limits indicate median values.</p

Kinetics of absolute numbers/µl blood of total and HCMV-specific CD4⁺ and CD8⁺ T-cells in four SOTR patients (each representative of one of the four patient groups).

<p>Patient A (group 1): no HCMV infection (no viral DNA) is detected and HCMV-specific CD4⁺ and CD8⁺ T-cells are consistently above the cut-off (black dotted line corresponding to 0.4 T-cells/µl blood); Patient B (group 2): self-resolving infection in the presence of low viral load and specific CD4⁺ and CD8⁺ T-cells consistently above the cut-off; Patient C (group 3): self-resolving infection in the presence of a high viral load peak and a number of HCMV-specific CD8⁺ T-cells above the cut-off, but in the absence of specific CD4⁺ T-cells or in the presence of CD4⁺ T-cells at a level close to the cut-off for the first two-three months after transplantation; Patient D (group 4): uncontrolled infection in the presence of high viral load above the cut-off (requiring antiviral treatment) and absence of specific CD4⁺ T-cells until 12 months after transplantation. The dashed line indicates the cut-off of viral load to start preemptive therapy. KTR, kidney transplant recipient; HTR, heart transplant recipient; VGCV, valganciclovir.</p

Kinetics of median levels of polyfunctional HCMV-specific CD8⁺ T-cells in groups 1–4 SOTR.

<p>No consistent statistically significant difference was observed between the four patient groups.</p

Polyfunctional hierarchy of HCMV-specific CD4⁺ T-cells in groups 1 and 2 SOTR.

<p>Predominance of polyfunctional vs monofunctional CD4⁺ T-cells in healthy controls and in protected patients of groups 1+2.</p

Characteristics of the 27 patients with primary HCMV infection.

<p>Characteristics of the 27 patients with primary HCMV infection.</p

Kinetics of median levels of (A) total and (B) HCMV-specific CD8⁺ T-cells in SOTR.

<p>No significant difference was found in the number/µl blood of HCMV-specific CD8⁺ T-cells among the different groups at any time post-transplant.</p

Kinetics of median levels of (A) Vδ2⁻ γδ T-cells and (B) Vδ2⁻/Vδ2⁺ γδ T-cell ratio.

<p>No significant difference was observed among groups in the number of Vδ2⁻ γδ T-cells. The Vδ2<b>⁻</b>/Vδ2⁺ γδ T-cell ratio was significantly higher in group 4 than in groups 1 and 3 at days 60 and 360. Stars above columns indicate significant differences among transplanted patient groups: *, P<0.05.</p