Other Blood Cells

At presentation, most patients have evidence of suppressed hematopoiesis. Abnormalities of monocytes, T cells, NK cells, dendritic cells, platelets, and neu-trophils have all been described in HCL.6 46 Among these, the monocytopenia of the disease and altered T-cell function have attracted particular attention because of their potential contribution to the marked immune deficiency present in active disease.

The cause of the almost complete absence of circulating monocytes remains unclear. It has been proposed that reduction in antigen presentation, as a result of monocytopenia and reduced numbers of den-tritic cells, is partly responsible for the defective immune responses in HCL. However, since tissue macrophages are plentiful,6 abnormalities of T cells and of their interactions with antigen-presenting cells seem to be of a greater importance. T-cell abnormalities include both quantitative and qualitative defects. Overall T-cell numbers are often reduced, the CD4+ / CD8+ cell ratio is reversed, and the percentage of 78 T cells is frequently increased.47-49 Moreover, the response of T cells to alloantigens in mixed lymphocyte cultures is grossly abnormal.48 49 This abnormality has been attributed to reduced or absent CD28 expression on a large proportion of CD4+, as well as CD8+ cells.49 Among CD4+ T cells, CD45RO+ memory cells are grossly reduced.50

Studies of the T-cell receptor (TCR) in HCL have demonstrated oligoclonality in most patients, with a markedly skewed repertoire of TCRpV genes.51 Moreover, some gene segments of the normal repertoire were absent from the T cells of HCL.4952 Interestingly, aIFN treatment leads to both the disappearance of the selected clones and to a gradual full restoration of the normal TCR repertoire,52 suggesting a direct influence of the malignant cells on T-cell development in HCL. Some of the apparently expanded clones are found to recognize antigens overexpressed by (but not necessarily specific to) HCs, as is the case with overexpressed synaptojanin 2.53 However, T cells that were found to be clonally expanded in HCL seem to have no cytotoxic effect on the malignant cells,54 and therefore are unlikely to have a beneficial effect on disease progression.

Thus, although abnormalities of the immune system in HCL have over the years received considerable attention, many questions regarding the immunobiol-ogy of the disease remain to be answered. It should be pointed out, however, that the clinical importance of the immune system dysfunction in HCL has been significantly reduced by the current successful early therapy of the disease.

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