CMV-Associated Expansion of CD8+CD45RA+CD27− T-Cells in Patients with B-Cell Malignancies.

Abstract

In patients with various malignancies of B-cell origin, changes in the T-cell compartment have been observed. In B-cell chronic lymphocytic leukemia (CLL), we have previously described an expansion of T-cells, largely due to an increase in T-cells exhibiting the CD45RA+CD27- effector phenotype. This was found only in cytomegalovirus (CMV) seropositive patients, suggesting that CMV-antigen drives this expansion. Indeed a considerable fraction of these T-cells were shown to be CMV-specific. At present it is unknown whether this alteration of the T-cell compartment is specific for CLL or rather any B-cell malignancy could induce similar changes. We performed an immunophenotypic analysis of the T-cell compartment in the peripheral blood of 56 patients with a B-cell malignancy (CLL, n=16; indolent lymphoma, n=20; aggressive lymphoma, n=10; multiple myeloma, n=10) and 12 healthy controls. Subjects of the different disease categories and controls were age-matched. We assessed the total CD3 compartment, naïve (CD27+CD45RA+), memory (CD27+CD45RA−) and memory effector (CD27−CD45RA+) CD8+ T cells. Latent CMV infection was assessed both by CMV-IgG titers (ELISA) and CMV viral load (PCR). The absolute number of T-cells was significantly increased (2.5 – 3 fold) in CLL, but not in the other B-cell malignancies. However, in all disease categories the CD4/CD8 ratio was decreased when compared to healthy controls. This was due to a slight decrease in CD4+ T-cells and an increase in CD8+ T-cells. Irrespective of the nature of the malignancy, the expansion of CD8+ T-cells resulted from a significant increase in CD45RA+CD27− effector T-cells. In agreement with our previous observation, CD8+ T-cell changes were only found in CMV-seropositive patients. Based on our earlier studies we expect these T-cells to be CMV-specific. No correlation between CMV-specific antibody titers and effector T-cell numbers was found. We conclude that the, possibly CMV-specific, effector T-cell compartment is expanded in all B-cell maligancies, although these changes seem to be more pronounced in CLL. The expansion of the total T cell compartment is restricted to CLL. The skewing of the T-cell compartment in CMV-seropositive patients could be the result of increased pressure of latent CMV-infection on the cellular immune system due to failure of other aspects of host defence, brought about by the malignancy.