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We describe a large-cell lymphoma of activated lymphoid cells in six children and adolescents. The presenting clinical features of regressing skin lesions and peripheral lymphadenopathy, sinus infiltration of lymph nodes, and infrequent tumor cell erythrophagocytosis resulted in initial diagnoses of malignant or regressing atypical histiocytosis in five cases. Binucleate and multinucleate tumor cells, sometimes with prominent eosinophilic nucleoli, resembled Reed-Sternberg (RS) cells and occasionally were found in a cytoarchitectural milieu that was consistent with a diagnosis of Hodgkin's disease (HD). The tumor cells did in fact express the HD-associated antigen Ki-1, but unlike most types of HD, the RS-like cells expressed common leukocyte antigen and were negative for Leu-M1. A T cell origin for the malignant cells was demonstrated with monoclonal antibodies in two cases, by focal staining for nonspecific esterase in one case, and by rearrangement of the beta- chain genes for the T cell receptor in a fourth case. These studies provide further evidence that some cases previously interpreted as malignant or regressing atypical histiocytosis and some types of HD are actually T cell disorders.

Peritoneal macrophages endocytosed their histocompatibility antigens (RT1), Fc receptors (FcR), and concanavalin A (Con A) receptors after cross-linking by ligands, but did not cap these membrane proteins. The 323N cell, a "macrophage like" tumor cell, under identical conditions capped its surface proteins. Experiments measuring fluorescence recovery after photobleaching showed that the mobile fraction of RT1 was significantly greater in 323N cells than in normal peritoneal macrophages. Presumably, the membrane proteins of 323N are not as tethered to the cytoskeleton, or, if so, are in a nexus that is not the same as that which occurs between membrane proteins of normal macrophages and the cytoskeleton. The mobility of RT1 on normal lymphocytes was also different from that of macrophages. These observations suggest that the movement of membrane molecules is determined by cell type and is regulated by the cytoskeleton which varies in structure and function from cell type to cell type.

Recently, 12 new transductions of c-erbB have been identified in a series of Rous-associated virus type 1-induced erythroleukemias. During the passage of these new transducing viruses it has become apparent that the erythroleukemia in chicken 5005 contained two different c-erbB transducing viruses. One induces erythroblastosis, whereas the second induces angiosarcoma. The angiosarcoma- and erythroblastosis-inducing viruses appear to have had a common ancestor, since tumors induced by each contain a novel, 4.3-kilobase c-erbB-related EcoRI fragment. The angiosarcoma-inducing virus has been named avian angiosarcoma virus and is designated for the chicken in which it originated.

The effect of natural killer (NK) cells on the course of acute and persistent murine cytomegalovirus (MCMV) infection was examined by selectively depleting NK cell activity by inoculation of mice with antibody to asialo GM1, a neutral glycosphingolipid present at high concentrations on NK cells. The dose of MCMV required to cause 50% mortality or morbidity in control C57BL/6 mice dropped 4- and greater than 11-fold, respectively, in mice first treated with anti-asialo GM1. NK cell-depleted mice had higher (up to 1,000-fold) virus titers in their lungs, spleens, and livers at days 3, 5, 7, and 9 postinfection. Spleens and livers of control mice were virus-free by day 7 postinfection, and their lungs showed no signs of active infection at any time. In contrast, MCMV had disseminated to the lungs of NK cell-depleted mice by day 5, and these mice still had moderate levels of virus in their lungs, spleens, and livers at day 9. Markedly severe pathological changes were noted in the livers and spleens of NK cell-depleted, MCMV-infected mice. These included ballooning degeneration of hepatocytes and spleen necrosis. MCMV-infected, NK cell-depleted mice had severe spleen leukopenia, and their spleen leukocytes exhibited a significantly lower (up to 13-fold) response to the T cell mitogen concanavalin A when compared with those of uninfected and MCMV-infected controls. It appeared that NK cells exerted their most potent antiviral effect early in the infection, in a pattern correlating with interferon production and NK cell activation; treatment with anti-asialo GM1 later in infection had no effect on virus titers. The relative effect of NK cell depletion on MCMV pathogenesis depended on the injection route of the virus. NK cell depletion greatly augmented MCMV synthesis and pathogenesis in mice inoculated either intravenously or intraperitoneally but had no effect on the course of disease after intranasal inoculation, at any time point examined. One month after intraperitoneal inoculation of virus, NK cell depletion resulted in a six- to eightfold increase in salivary gland virus titers in persistently infected mice, suggesting that NK cells may be important in controlling virus synthesis in the salivary gland during persistent infection. This treatment did not, however, induce dissemination of virus to other organs. These data support the hypothesis that NK cells limit the severity, extent, and duration of acute MCMV infection and that they may also be involved in regulating the persistent infection.

Established subcutaneous Moloney sarcomas (MST-1) of large size and long duration were eliminated from syngeneic rats by intravenous infusion of varying numbers of specific syngeneic effector T lymphocytes. Spleen cells from BN rats in which tumor had regressed were cultured in an in vitro mixed lymphocyte tumor cell culture (MLTC) to augment cytotoxicity of effector cells. In the MLTC a T cell subset was expanded in response to MST-1 antigens and transformed into blast elements. With these changes, there was an increase in the W3/25 antigen on the T cell surface, a decrease of W3/13 antigen, and an increase in the number of T cells with Ia antigens. The subset associated with elimination of established tumors was a blast T cell W3/25+, W3/13+, as detected by monoclonal antibodies to rat T antigens. The W3/25+ subset was poorly cytotoxic in vitro for MST-1 and apparently functioned in vivo as an amplifier or helper cell in the tumor-bearing host. The W3/25- population was a melange of cells that included (W3/13+, W3/25-) T cells, null cells, Ig+ cells, and macrophages, and was associated with enhancement of tumor in vivo, suggesting the presence of suppressor cells.

The rate of capping and shedding of cross-linked surface immunoglobulins (SIg) was slower in old Lewis rats (greater than 24 mo) than in young Lewis rats (3-4 mo). Analysis of spleen cell populations with the fluorescence-activated cell sorter indicated that with aging there was a loss of cells with a high density of SIg. Cells with the highest density of SIg capped and shed cross-linked SIg faster than cells with a low density of SIg. The alteration in density of SIg may account for the difference in capping kinetics. Colchicine treatment increased the rate of capping of lymphocytes from young animals, but had no effect on the capping kinetics of lymphocytes from old animals.