Human CD4+ CD25 high cells suppress proliferative memory lymphocyte responses to herpes simplex virus type 2

Abstract

Lymphocytes with the regulatory CD4+ CD25+ phenotype frequently suppress memory T-cell responses. Murine herpes simplex virus type 1 (HSV-1) models have shown that CD4+ CD25+ cells can limit immunity-mediated corneal damage but slow viral clearance. We investigated the effect of CD4+ CD25+ cells from healthy HSV-2-infected humans on recall proliferative (CD4) responses to HSV-2. Depletion and reconstitution experiments were consistent with a suppressive effect of autologous blood-derived CD4+ CD25+ cells for whole HSV-2 antigen. Regulatory T cells may modulate human CD4 memory responses to HSV-2 and influence their antiviral and inflammatory functions.

FIG. 1.

CD4 and CD25 staining for CD14⁻ lymphocyte-gated, freshly prepared PBMC. Results are from a typical subject. The percentages of cells in the indicated regions are listed. The left panel is before sorting of cells; the middle and right panels are analyses of sorted CD4⁺ CD25^low and CD4⁺ CD25⁺ cells, respectively.

FIG. 2.

Effect of depletion and addition of CD4⁺ CD25⁺ cells on [³H]thymidine incorporation proliferative responses to whole HSV-2 and CMV recall antigens in seropositive donors and to PHA. Data for CD25 depletion (solid bars) are the differences between the mean counts per minute for CD25-depleted CD4 responder cells minus the mean counts per minute for unsplit CD4 responder cells. Data for CD25 add-back experiments (open bars) are the differences between the mean counts per minute for CD4 responder cells with CD4⁺ CD25⁺ cells added back minus the mean counts per minute for CD4 responder cells depleted of CD4⁺ CD25⁺ cells. The same eight subjects are presented in order for HSV-2 and PHA. For the six CMV-seropositive subjects, the subject numbers corresponding to the HSV-2 and PHA data are shown.