T-cell response to viral antigens in adults and children with common variable immunodeficiency and specific antibody deficiency

Abstract

Several T cell abnormalities have been described in common variable immunodeficiency (CVID), a B cell disorder of mainly unknown origin. A subset of CVID patients suffers from frequent reactivations of herpes viruses. We studied T cell function in CVID [and in a subset of paediatric patients with specific antibody deficiency (SAD)] by measuring T cell proliferation and cytokine production in response to herpes virus-antigens in paediatric CVID patients (n=9) and paediatric SAD patients (n=5), in adult CVID patients (n=14) and in healthy controls. Paediatric CVID patients, but not SAD patients, displayed moderately increased CD8+ T cell proliferation in response to cytomegalovirus, human herpes virus type 6B (HHV6-B) and herpes simplex virus compared to controls. CD8+ T cell responses in adult CVID patients tended to be increased in response to cytomegalovirus and herpes simplex virus. In response to stimulation with herpes virus antigens, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha and interferon inducible protein (IP)-10 were produced. Overall, no major differences were detected in cytokine production upon stimulation between patients and controls, although higher IL-10 and IL-12 production was detected in paediatric patients. In conclusion, cellular immunity against herpes virus antigens appears undisturbed in CVID patients, although defects in subpopulations of CVID patients cannot be excluded.

Fig. 1

Virus-specific CD4⁺ and CD8⁺ T cell proliferation. (a) Representative fluorescence activated cell sorter (FACS) plots of antigen-specific T cell proliferation of a control (upper panel) and a common variable immunodeficiency (CVID) patient (lower panel). Cells were gated in lymphocyte morphology based on forward- and side-scatter and the expression of CD3. Percentages of proliferating CD8⁺ T cells are shown in the upper left corners, whereas percentages of proliferating CD4⁺ T cells are presented in the lower left corners. Shown are responses to medium alone, the cytomegalovirus (CMV) matrix protein pp65, the CMV immediate early antigen (IE)1, HSV type I antigen and concanavalin A. Bars indicate the median (with interquartile range) of the stimulation index (SI) of paediatric CVID patients compared to age-matched controls (b), of pediatric SAD patients compared to age-matched controls (c) and of adult CVID patients compared to adult controls (d). Black: CVID; white: controls. P-values < 0·05 are considered significant (Mann–Whitney U-test) and indicated with an asterisk.

Fig. 2

Cytokine production in response to the different viral antigens. Interleukin (IL)-10 production in response to different viral antigens in common variable immunodeficiency (CVID) patients and children with specific antibody deficiency (SAD) (depicted by triangles) and control groups (median with range). P-values < 0·05 are considered significant (Mann–Whitney U-test).