Antigenic differences between human platelets and megakaryocytes.

To investigate the apparent paradox in the observation that most patients with immune thrombocytopenias have normal or increased numbers of megakaryocytes (MKs), the extent of antigenic cross-reactivity between normal platelets and MK was examined. Indirect immunofluorescence and ultrastructural studies were carried out by means of four antisera specific for platelets: anti-GpIb, anti-GpIIb/IIIa, anti-PLA1, and an antiserum from a patient with quinidine-induced thrombocytopenia. Following incubation of freshly collected marrow with these antisera, MK were first identified by phase-contrast microscopy and then inspected for fluorescence. Almost all MKs were found reactive with the last three antisera, albeit to a variable extent. In contrast, only 24% reacted with anti-GpIb. The pattern of fluorescence, ie, rim, partial or cytoplasmic, appeared to be related to the extent of MK fragmentation. Only rim fluorescence of living MKs could be interpreted to indicate that the platelet epitope was exposed on the surface of the precursor cell. The observations suggest that platelet antigens are variably expressed on the plasma membranes of MKs. In a clinical setting, the heterogeneity among platelet target antigens and the extent to which these are exposed on MKs at various stages of maturation may dictate the severity of the thrombocytopenia and degree of ineffective thrombocytopoiesis.     

Megakaryocyte and platelet structure in thrombocytopoiesis: the effect of cytokines

This paper presents an overview of selected data which the author considers crucial to an understanding of structure/function relationships of megakaryocytes (MK) and platelets. The observation that platelet territories form within the MK cytoplasm and that, therefore, MK and platelet plasma membranes need not be structurally or antigenically identical is substantiated on the basis of results obtained with a variety of experiments. While the predominant site of MK fragmentation is still debated, it is generally accepted that such terms as "proplatelets," "giant platelets" or "megathrombocytes" refer to MK fragments consisting of more than one platelet territory. It is suggested that such fragments be called "compound" platelets to convey a unifying concept. The terms "young" or "immature" could be reserved for platelets which still contain ribosomes, rough endoplasmic reticulum or other organelles not usually seen in circulating platelets. Finally, the structure changes induced by cytokines, such as interleukin 3 (IL-3), IL-6, IL-11 and thrombopoietin have been illustrated.     

Human T-Cell Lymphotropic Virus Type 1 Tax among American Blood Donors

In the United States, all blood used for transfusion is tested for the presence of antibodies to the structural components of the human T-cell lymphotropic viruses types 1 and 2 (HTLV-1 and -2). Based on such serologic tests, the prevalence of HTLV-1 infection is estimated to range from 0.016 to 0.1%. As a consequence of studies of patients with mycosis fungoides and some of their healthy relatives who are antibody negative but were found to carry the tax sequence of HTLV-1 in their lymphocytes and who had antibodies to the p40^tax protein, a study was undertaken to determine the prevalence of the “tax-only” state in 250 healthy blood donors and other volunteers. Using PCR and Southern analysis for cell lysates and using Western blotting for plasmas, 8.6% of the blood donors proved to be tax sequence positive and antibody positive. Sequence analysis of specimens from 22 individuals proved that 20 of the sequences were homologous with that of HTLV-1 while 2 resembled the HTLV-2 sequence. The latter were obtained from volunteers of Indian origin. The possible clinical significance of the tax-only carrier state is discussed.     

Interaction of human immunodeficiency virus type 1, human T-cell leukemia/lymphoma virus type I (HTLV-I), and HTLV-II with in vitro-generated dendritic cells.

Although it is known that impairment of dendritic cells (DC) plays a role in the pathogenesis and immunosuppression of retrovirus-associated diseases, it is not clear whether, or to what extent, these antigen-presenting cells themselves become infected. The realization that the cells can be generated in vitro in larger numbers than can be isolated from circulating blood or bone marrow raised the possibility that they could be used for therapeutic purposes. Therefore, we investigated whether DC generated in vitro from CD34 precursors are susceptible to infection when cocultured with human immunodeficiency virus type 1- or human T-cell leukemia/lymphoma virus-infected cell lines. While there appears to be a remarkable affinity of the viruses for the plasma membranes of the DC, interiorization or budding was not observed in 30 experiments carried out under a variety of conditions.     

Ultrastructural, Immunologic, and Functional Studies on Sézary Cells: A Neoplastic Variant of Thymus-Derived (T) Lymphocytes

The vast majority of human lymphoid neoplasms examined to date have been associated with a proliferation of bone marrow-dependent (B) lymphocytes. In an effort to delineate human tumors of T-cell (thymusdependent) lineage, use was made of the peripheral blood leukocytes of sixteen subjects with various forms of mycosis fungoides. The abnormal cells in the circulation of these patients are morphologically identical to those that infiltrate their nodes and skin. On electron microscopy, such neoplastic lymphocytes (Sézary cells) had "cerebriform" nuclei and an abundance of cytoplasmic fibrils not described heretofore. Sézary cells were nonadherent and nonphagocytic and usually responded to stimulation with phytohemagglutinin, refuting earlier suggestions that the cells represent monocytes or histiocytes. In contrast to chronic lymphocytic leukemia lymphocytes, the Sézary cells lacked surface immunoglobulin and receptors for complement. Ultrastructural analysis identified Sézary cells in the center of directly formed rosettes (E-rosettes) characterizing the behavior of T lymphocytes in this test. Though some Sézary cells lacked both T and B cell-surface properties, in general, these observations support the view that the Sézary cell is a neoplastic variant of a thymusderived lymphocyte.