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A nonglycosylated denatured form of human immunodeficiency virus (HIV) 1 glycoprotein gp120 (Env 2-3), which does not bind to CD4, was used with muramyl tripeptide as adjuvant to immunize HIV-seronegative healthy volunteers. In all the volunteers, three 50-micrograms injections of Env 2-3 induced priming of CD4+ T cells specific for conserved regions of the native glycosylated gp120. Moreover, we found that several major histocompatibility complex class II (DR) alleles can function as restriction molecules for presentation of conserved epitopes of gp120 to T cells, implying that a T-cell response to these epitopes can be obtained in a large fraction of the population. The possibility to prime CD4+ T cells specific for conserved epitopes of a HIV protein is particularly important in view of the lack of such cells in HIV-infected individuals and of a possible role that CD4+ T cells may play in the development of protective immunity against AIDS.

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The production of tumor necrosis factor alpha (TNF alpha) and interleukin 1 (IL-1) was measured in supernatants of cultured peripheral blood monocytes that were obtained from patients with human immunodeficiency virus type 1 (HIV 1) infection and that were purified by counterflow centrifugal elutriation (86-92% purity). TNF alpha levels were significantly higher in monocytes isolated from symptomatic HIV 1-infected patients as compared to normal controls. Although IL-1 levels were also elevated in this group of symptomatic patients they did not reach statistical significance. The production of the two monokines was intermediate in asymptomatic HIV 1-infected individuals. The increase of TNF alpha was observed in the absence of in vitro stimulation as well as in the presence of interferon-gamma plus lipopolysaccharide. TNF alpha and IL-1 were measured by radioimmunoassay and by bioassay, the results of the two methods being highly correlated for both cytokines. The levels of TNF alpha and IL-1 were also positively correlated. These data suggest that IL-1 and TNF alpha may be involved in the pathogenesis of HIV 1 infection.

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A brief overview is presented of the different antinuclear autoantibodies most frequently mentioned in the literature at the present time. The relationship between these autoantibodies and collagen diseases is described in terms of their usefulness in diagnosis and follow-up. Lupus anticoagulant is also mentioned in view of its possible relationship with anti-DNA autoantibodies.

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Immunotactoid glomerulopathy is a recently described entity characterized clinically by proteinuria, hematuria and hypertension, and on renal biopsy by various glomerular lesions including extracellular microtubules composed of immune reactants. Furthermore a defined immunological disease or cryoglobulinemia are absent. We report the case of a patient with immunotactoid glomerulopathy and hypocomplementemia (low C3 level) who developed several episodes of leucocytoclastic skin vasculitis with large immune deposits in and around small vessels. It is suggested that skin and renal involvement are part of the same systemic disease.

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Purified lymphocyte and monocyte populations were obtained from peripheral blood cells by ficoll-hypaque gradient and elutriation in different normal individuals. The two types of mononuclear cells were then analyzed by 2-dimensional gel electrophoresis. More than 1,000 spots were detected by our computer system and analyzed for each cell type. Automatic picture comparison showed a typical pattern for the two different populations with excellent reproducibility.

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Interleukin 1 (IL-1) possesses multiple biological activities that may be blocked selectively by different inhibitors. Some known inhibitors block the lymphocyte activating factor (LAF/IL-1) but not the mononuclear cell factor (MCF/IL-1) measured by its capacity to stimulate prostaglandin E2 (PGE2) and collagenase production. The presence of IL-1 in vivo may be difficult to detect due to the presence of inhibitor(s) and the level of the inhibitor(s) may vary depending upon pathological conditions. We have found that urine from three patients with monocytic leukemia (M5) contained high levels of inhibitor(s) of MCF/IL-1, whereas urine of normal subjects did not contain significant amounts. Urine from two patients with other blood neoplasic diseases also contained little inhibitory activity. The MCF/IL-1 inhibitor(s), which also acts on human recombinant IL-1 beta, is approximately 25-35 kD, is not retained on concanavalin A-Sepharose column and can be partially destroyed with urea and boiling. At this stage of the purification the fraction containing the MCF/IL-1 inhibitor(s) also inhibits the LAF/IL-1 assay. However, this inhibitor(s) is probably distinct from other inhibitors already described.

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The relative importance of polyclonal B cell activation has been studied in relation to the development of autoantibodies in human African trypanosomiasis. In 34 patients investigated before specific treatment a broad expression of the B cell repertoire was observed including the production of anti-hapten (FITC, Penicillin, Phosphorylcholin) antibodies, of high levels of antibodies against some heterologous protein antigens (ovalbumin and tetanus toxoid) and of autoantibodies. Anti-ssDNA antibodies were detected in 84% of the patients and anti-IgG rheumatoid factors in 88%. Anti-striated muscle and anti-smooth muscle antibodies were also observed in 57 and 63% of the patients. Correlation analysis indicated that the formation of anti-DNA antibodies is associated with polyclonal B cell activation but probably depends on an additional B cell stimulation by released DNA or cross-reacting antigens. Anti-immunoglobulin antibodies are closely correlated with polyclonal B cell activation and their production is likely to reflect the high frequency of anti-IgG B cell precursors in the normal human B cell repertoire. The significance of these observations in relation to the pathological expression of trypanosomiasis should be particularly considered in the generation of immune complexes either in circulating blood or locally at the sites of parasite destruction.

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Circulating autoantibodies directed at creatine kinase (CK) BB isozyme are detected in plasma in the form of an immune complex (immunoglobulin CK BB) termed macro-CK type 1. Fourteen patients presented a falsely elevated CK MB isozyme fraction as measured by the immunoinhibition method; they were found to have IgG-CK BB complexes, which was considered to be indirect evidence of circulating anti-CK BB autoantibodies. No evident clinical association between the detection of this autoantibody in complexed form and autoimmune disease could be established, there was no significantly increased incidence of other autoantibodies, and there was no specific alteration in immunoglobulin and complement levels; however, the HLA haplotype A1,B8,DR3, which is known to be associated with autoimmunity, was present in five patients.

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Both interferon-gamma (IFN-gamma) and 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) induce changes in the human monocytic cell line U937 that may reflect cellular differentiation. The effects of recombinant IFN-gamma and 1 alpha,25(OH)2D3 on U937 cells with regard to the release of superoxide anion (O2-), prostaglandin E2 (PGE2), and mononuclear cell factor (MCF) after stimulation with phorbol myristate acetate (PMA) were examined. PMA did not induce O2- production in untreated cells. A 3-day preincubation with IFN-gamma or 1 alpha,25(OH)2D3 resulted in a 5- to 10-fold increase in PMA-stimulated production of O2- as compared to cells preincubated in medium alone. The response was related to IFN-gamma and 1 alpha,25(OH)2D3 concentrations. In contrast, the PMA-induced production of PGE2 and MCF does not require preincubation with either IFN-gamma or 1 alpha,25(OH)2D3. These results suggest that O2- production and cytokine production (i.e., PGE2 and MCF) are modulated by different signals related to maturation processes.

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Lymphocytes influence the production of both prostaglandin E2 (PGE2) and interleukin 1 (IL 1) by monocytes. We have examined whether these two products are released concomitantly or not under identical culture conditions using monocyte- and lymphocyte-enriched populations obtained on Percoll gradient. IL 1 was measured as mononuclear cell factor (IL 1/MCF). When incubated with concanavalin A, the monocyte-enriched fraction (MF; 80-91% monocytes), but not the lymphocyte-enriched fraction (LF; 95% lymphocytes) produced increasing amounts of PGE2 and MCF. However, when LF cells were added to MF cells in culture, a 40% to 60% decrease of PGE2 secretion was observed whereas the MCF production remained unchanged or increased up to 26-fold. Such a dissociation between IL 1 and PGE2 production by monocytes indicates independent regulation mechanisms in controlling the immune response under the influence of lymphocytes.

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Monocytes and polymorphonuclear leukocytes from normal blood donors phagocytosed preferentially Plasmodium falciparum-infected red blood cells (IRBC) in presence of sera from individuals living in areas endemic for malaria. Total complement or factor B heat inactivation of immune or normal serum does not alter opsonic activity directed against IRBC.

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Peripheral blood monocytes from 10 systemic lupus erythematosus (SLE) and 10 rheumatoid arthritis (RA) patients as well as from 24 controls were studied for such functions as phagocytosis, bactericidal capacity, iodination, and PGE2 production. Phagocytosis of opsonized erythrocytes, exploring only the Fc receptor, was increased in SLE and RA. Killing of Staphylococcus aureus was decreased in both SLE and RA in the presence of AB serum, but not in the presence of autologous serum. Iodination was, on the average, normal in SLE and elevated in RA. Prostaglandin E2 production was decreased in SLE (except with the highest concentration of Con A) and increased in RA. In SLE, functional alterations were more pronounced in clinically active than in inactive disease. These results show that in SLE and RA peripheral blood monocytes have alterations of their functions that are independent of serum factors. It is suggested that these abnormalities may be relevant to the pathogenetic mechanisms and evolution of these diseases.

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A method is described for the visualization of red blood cells infected with Plasmodium falciparum ingested by monocytes or polymorphonuclear leukocytes (PMN) after in vitro incubation. Smears were stained with peroxidase followed by 4,6-diamino-2-phenylindole (DAPI) staining specific for DNA. Monocytes or PMN were identified under normal illumination by the peroxidase stain and the nuclei of these cells as well as the parasites were identified by means of the DAPI stain with ultraviolet light. Using this method we found that monocytes and PMN from normal blood donors preferentially phagocytose plasmodium falciparum infected red blood cells in the presence of sera from subjects living in areas endemic for malaria.

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Polymorphonuclear leukocytes (PMN) from normal blood donors phagocytosed P. falciparum-infected red blood cells (IRBC) to a greater extent than normal RBC under in vitro culture condition. The phagocytic activity of PMN was greatly increased by the addition of sera from individuals living in areas endemic for malaria (immune sera) but not by sera from individuals recovering from a first acute P. falciparum infection. The enhancement of the phagocytic activity was associated with the purified IgG fraction of immune sera and was lost after absorption of IgG on protein A sepharose column of preincubation of the immune sera with IRBC. These experiments suggest that opsonisation of IRBC and their subsequent phagocytosis may be one of the mechanisms involved in the clearance of P. falciparum infection in individuals living in areas endemic for malaria.

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In vitro human monocytes from normal blood donors ingest red blood cells infected with Plasmodium falciparum more efficiently than normal red blood cells (NRBC). The phagocytic activity of human monocytes for infected red blood cells (IRBC) is greatly enhanced by the addition of immune sera obtained from individuals living in areas with endemic malaria. In contrast, the addition of sera obtained from individuals recovering from a first infection, or pooled normal sera, does not result in increased phagocytosis of IRBC. The phagocytosis enhancing activity of immune sera is associated with the IgG fraction and IgG depleted sera do not stimulate phagocytosis. Enhanced immune serum mediated phagocytosis occurs as a result of opsonization of IRBC. This was demonstrated by experiments in which monocytes or IRBC were preincubated with immune serum prior to the phagocytic assay. The opsonic activity could be absorbed by IRBC but not by NRBC. The opsonization of IRBC and subsequent phagocytosis were also dependent on the stage of development of the intracellular parasite. IRBC containing schizonts and trophozoites were preferentially phagocytosed as compared with ring forms. The role of malaria induced surface alterations and/or malaria surface antigens in the opsonization of IRBC by immune sera is discussed. These experiments suggest that phagocytosis of P. falciparum IRBC by monocytes may play a role in the immune elimination of malaria infection in humans.

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The level of ferritin and circulating immune complexes (IC) were measured in 53 patients with solid tumors and metastasis using C1q binding assay and the conglutinin binding assay. The level of circulating IC was increased in patients (p less than 0.001) as compared to the controls. Ferritin level was increased in both male and female patients (p less than 0.001), even when the ferritin value was corrected by the aspartic transaminase value, to take for hepatic damage in account. Ferritin was not found to be an important component of immune complexes as IC ferritin did not exceed 2 per cent of total serum ferritin in the 10 patients that were investigated. These results suggest that ferritin levels and circulating IC were increased in patients with solid tumors and metastasis, but that these two parameters are not correlated.

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111 patients with acute leukemia, including 29 children, were classified according to the surface markers and cytochemistry of their blasts. The acute leukemias were separated into two majors groups (lymphoid and non-lymphoid) depending on the presence or absence of specific lymphoid markers. On the basis of these criteria a correlation of 94% with the hematological diagnosis was obtained. Acute lymphoblastic leukemia (ALL) was divisible into three sub-groups: 11 cases expressing T-cell specific markers were classified as T-ALL and 33 cases expressing the common ALL antigen (CALLA) as c-ALL. 18 of the latter expressed an additional marker, DSA (Daudi surface antigen), splitting c-ALL cases in two subgroups. Cytochemistry of the cases lacking specific surface markers (n = 67) served to diagnose 41 acute myeloid leukemia (AML) cases and 8 monoblastic leukemias. The remaining 18 cases could not be classified. The presence of absence of HLD-DR (Ia) antigens served to subdivide AML into two major subgroups. The prognostic significance of these new diagnostic splits is under active study.

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