Cytomegalovirus (CMV) infection in AIDS patients is associated with a CD3 receptor-mediated T cell hyporesponsiveness

Abstract

HIV+ individuals with human CMV (HCMV) reactivation have a CD3 receptor-mediated T cell hyporesponsiveness when compared with CD4-matched HIV+ and HCMV- control groups. The impairment of proliferation was not reversed by exogenous IL-2. A typical increase in NFkappaB expression was observed following cross-linking of the CD3 receptor, but did not lead to increased CD25 cell surface expression or cell proliferation. The HCMV-induced non-responsiveness was not observed when cells were stimulated with phorbol esters. Lymphocytes cultured with media collected from cell cultures infected with HCMV showed a dose-dependent inhibition in the total T cell population even though cells staining dually for CD8/57 increased in number. The altered growth factor requirements of CD8/57+ cells may therefore account for their presence in AIDS and patients following bone marrow transplantation.

Fig. 1

A box and whiskers plot of the effect of human CMV (HCMV) infection on anti-CD3 stimulation on peripheral blood mononuclear cells. Details of the groups are given in Patients and Methods. Cells from normal HIV⁻ donors stimulated with anti-CD3 and cultured with 25% HCMV-conditioned media are shown in group 4a. The box represents the interquartile range and the whiskers are lines that extend from the box to the highest and lowest values excluding outliers. Outliers (○) are samples with values between 1.5 and 2.5 box lengths from the upper or lower edge of the box.

Fig. 2

(a) Flow cytometric analysis of cells cultured with human CMV (HCMV)-conditioned media showed a dose-dependent inhibition in CD3 and CD8 lymphocytes compared with media alone (at 25% P < 0.05). (b) Dual staining of CD8 cells for CD57 expression revealed a significant increase in the number of CD8/57⁺ lymphocytes. At 25% HCMV-conditioned media a six-fold increase was detected over the media alone control (P < 0.05).

Fig. 3

Agarose gel electrophoresis of polymerase chain reaction (PCR) products from groups 1, 2 and 3 are shown. Amplification of β-actin was used to confirm integrity of isolated RNA and efficiency of the PCR. The expected product sizes for β-actin and NFκB were 1000 bp and 500 bp, respectively. The molecular weight marker (M) was a Hind III digest of λ phage DNA.