Loss of cytomegalovirus-specific immunological memory in a patient with thymoma

Abstract

Cytomegalovirus (CMV) retinitis is a re-activation infection associated with severely impaired T cell-mediated immunity. We describe a patient with long-standing Crohn's disease and thymoma who developed severe CMV retinitis. While thymoma can be associated with impaired humoral immunity and a quantitative CD4+ T helper cell deficiency, these were not evident in our patient. However, more detailed investigation of anti-CMV responses showed absence of specific T cell responses to CMV antigen. Normal CMV seropositive controls have detectable proliferation and interferon-gamma production by T cells in response to stimulation with CMV antigen, but this was absent in this patient both during the acute infection and in convalescence. Other measures of T cell function were normal. Since CMV retinitis is due to reactivation of latent CMV infection, it appears that selective loss of CMV-specific immunity had occurred, perhaps secondary to a thymoma. The causes of thymoma-associated immune impairment are not understood, but this case demonstrates that selective defects can occur in the absence of global T cell impairment. Opportunistic infections should therefore be suspected in patients with thymoma even in the absence of quantitative immune deficiencies.

Fig. 1

Proliferation of the patient's lymphocytes (filled symbols) in response to (a) mitogens, (b) candida antigen and (c) CMV antigen. Dilutions of each mitogen are indicated. ▪ PHA 250 μg/ml; • PWM 100 μg/ml; ♦ OKT3 1 μg/ml. Mean ³H thymidine incorporation (±SEM) is expressed as disintegrations per minute. T cell proliferative responses of a CMV seronegative control (□) and a CMV seropositive control (○) are also shown for Candida and CMV antigens. All of the patient's mitogen proliferation responses were equivalent to or greater than normal control responses (not shown).

Fig. 2

IFN-γ production by T cells on incubation with (a) SEB or (b) CMV antigen. Both seropositive and seronegative normal donors and the patient show normal IFN-γ production on stimulation with SEB. IFN-γ production is also induced by stimulation with CMV antigen in a normal CMV seropositive donor, but not in a normal seronegative donor. The seropositive patient showed no induction of this cytokine. Figures are gated on CD4+ and CD8+ T cells. CD69 expression identifies activated T cells.