Several properties of 10 cell lines derived from the polyoma-induced PW20 Wistar-Furth rat renal sarcoma have been examined, including the ability of the tumor cells to metastasize spontaneously from subcutaneous sites in syngeneic hosts, the platelet-aggregating activity of material extracted by urea from the surface of cultured cells, the sialic acid content of the platelet-aggregating material, and the degree of sialylation of cell surface glycoconjugates in cultured cells. A correlation has been observed among all of these parameters. The results suggest a possible link between the degree of cell surface sialylation of tumor cells, their ability to aggregate platelets, and their ability to metastasize. (7,8).In this paper we report the platelet-aggregating activity of the PAM extracted from cells of 10 derivatives of the polyoma-induced PW20 Wistar-Furth rat renal sarcoma cell line, which vary in their ability to metastasize spontaneously from subcutaneous sites of tumor growth (9). The PAM's activity was found to correlate positively with the propensity of the cells to metastasize. In addition, the PAM's activity correlates with the sialic acid content of the PAM and with the degree of cell surface sialylation of the cultured tumor cells. METHODSCell Lines. The PW20 family of tumor cell lines (Table 1) was derived from a culture of the polyoma virus-induced PW20 Wistar-Furth rat renal sarcoma (obtained from H. 0. Sjbgren, Univ. of Lund, Sweden) by varying conditions of passage in tissue culture and passage through syngeneic animals (9). The RO(L) and RO(H) cell lines represent low and high tissue culture passages, respectively, of the original cell culture. The R1 cell line was obtained by reestablishing a subcutaneous RO(L) tumor in tissue culture and maintaining the culture for a large number of passages. The R2 cell line was similarly produced by reculturing a subcutaneous R1 tumor and maintaining the resultant culture for a prolonged period. The RO(L)R1, RO(H)R1, R2R1, and R2R2 cell lines were produced by reculturing subcutaneous RO(L), RO(H), R2, and R2R1 tumors, respectively; the R2L1 and R2N1 cell lines were obtained by culturing explanted lung (L) and lymph node (N) metastases that developed from subcutaneous R2 tumors. These last-named lines were all tested at low passage numbers. In vttro assays were performed with cells within several passages of those listed in The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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In 1987, exploratory clinical studies were initiated to determine whether the development of AIDS in HIV-infected individuals might be delayed or prevented by immunization with an inactivated HIV preparation. Preclinical studies had shown the preparation to be safe and immunogenic. Twenty-three patients with biopsy-confirmed persistent generalized lymphadenopathy (CDC III) and two with asymptomatic HIV infection and CD4 lymphocyte counts between 135 and 769/mm3 were studied, of whom eight (32%) had additional HIV-related symptoms. Over a 3-year period, they received a median of eight open-label inoculations of 100 micrograms of inactivated gp 120-depleted HIV-1 Immunogen in incomplete Freund's adjuvant (IFA). Clinical, general laboratory, immunologic, and virologic parameters were followed for up to 6 years. No serious treatment-related adverse experiences were reported, nor was accelerated HIV disease progression seen. Twelve patients developed a delayed-type hypersensitivity response (HIV-DTH) to the immunogen and nine showed fourfold or greater increases in anti-p24 antibody titers. In the follow-up period, 10 of the 25 patients developed AIDS and one with Kaposi's sarcoma (KS) at baseline progressed. Of the 12 patients who became HIV-DTH-responsive, one developed an opportunistic infection (OI), occurring approximately 5 years from study onset, and subsequently died. One additional HIV-DTH responder developed KS. Of the 13 patients who remained HIV-DTH-nonresponsive, nine (69%) progressed to AIDS and seven of these have died. Differences were also observed in terms of HIV-DNA copy number, CD4 percentages, and anti-p24 antibody patterns between the HIV-DTH-responsive and -nonresponsive groups, suggesting a more favorable clinical course in the former. HIV-1 Immunogen in IFA appears to be safe and immunogenic. Further studies are indicated to determine clinical efficacy of the HIV Immunogen as well as the significance of the apparent correlation between HIV-DTH responsivity and a more favorable clinical course.

No abstract

The network theory of autoimmunity is presented with recent experimental data relevant to the understanding of the pathogenesis of AIDS. Schematically, effector T cells specific for self-antigens exist normally, but their activity is modulated and prevented by networks of regulatory T cells. As a result of mimicry between molecular components of microorganisms and self-antigens, autoimmune disease can be triggered by specific foreign pathogens which alter the state of activity of the network from suppression to activation. Conversely, by a procedure known as T-cell vaccination, autologous effector T cells re-injected after in vitro stimulation and attenuation may alter the state of the network from an activation to a suppression. Numerous observations are reviewed that support the concept of autoimmune activity in the destruction of non-infected T4 cells. Such activity is presumed to be triggered by an antigen of viral origin, the most likely, but not the only one, being the envelope protein gp 120. Based on this hypothesis, a T-cell vaccination procedure against effector T cells responsible for autoimmunopathic activity in HIV-seropositive patients is proposed, similar to the one known from experimental study of autoimmunity and presently being tested in human autoimmune diseases. Its purpose would be to prevent T-cell loss and the onset of immunodeficiency disease in HIV-seropositive patients. Apart from its potential therapeutic value, this procedure will have use as a therapeutic test from which insight will be gained about the immunopathogenesis of AIDS.