Progression to CMV end-organ disease in HIV-1-infected individuals despite abundance of highly differentiated CMV-specific CD8 + T-cells

Since CMV-specific T-cells have been shown to generally express an advanced state of differentiation, we investigated whether these mature CMV-specific T-cells are sustained in HIV-infected patients, who are not treated with HAART, receive no CMV medication, but do progress to AIDS with CMV end-organ disease (AIDS-CMV). CD8 + and CD4 + T-cell phenotype was studied in these patients in comparison with long-term asymptomatic HIV-infected individuals, progressors to AIDS without CMV end-organ disease as well as CMV-seropositive HIV-negative controls. CMV-specific CD8 + T-cells from progressors to AIDS-CMV expressed markers typical of highly differentiated effector T-cells, being CCR7 −, CD27 − CD45RO +/−, with high CD57 expression and increased Ki67 expression, compatible with functional effector cell capabilities. In addition, CD4 + T-cells with the characteristic CD27 −CD28 − phenotype previously shown to be induced by CMV infection specifically, were found in very high numbers in the HIV + individuals, but the highest in progressors to AIDS-CMV just before onset of disease. Also the normally rare CD45RO −CD27 −CD4 + subset increased significantly, whereas the CD45RO −CD27 +CD4 + subset decreased. Our data show that in patients progressing to AIDS-CMV, CMV-specific CD8 + T-cells have expanded and are fully differentiated to mature functional effector T-cells. These cells are not protective apparently, but may contribute to tissue-associated immunopathology characteristic of these clinical conditions.