Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old1. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass2,3 in the local Universe. What slowed down black-hole growth, leading towards the symbiotic growth observed in the local Universe, and when this process started, has hitherto not been known, although black-hole feedback is a likely driver4. Here we report optical and near-infrared observations of a sample of quasars at redshifts 5.8 ≲ z ≲ 6.6. About half of the quasar spectra reveal broad, blueshifted absorption line troughs, tracing black-hole-driven winds with extreme outflow velocities, up to 17% of the speed of light. The fraction of quasars with such outflow winds at z ≳ 5.8 is ≈2.4 times higher than at z ≈ 2-4. We infer that outflows at z ≳ 5.8 inject large amounts of energy into the interstellar medium and suppress nuclear gas accretion, slowing down black-hole growth. The outflow phase may then mark the beginning of substantial black-hole feedback. The red optical colours of outflow quasars at z ≳ 5.8 indeed suggest that these systems are dusty and may be caught during an initial quenching phase of obscured accretion5.

The rapid assembly of an elliptical galaxy of 400 billion solar masses at a redshift of 2.3.

Stellar archaeology shows that massive elliptical galaxies formed rapidly about ten billion years ago with star-formation rates of above several hundred solar masses per year. Their progenitors are probably the submillimetre bright galaxies at redshifts z greater than 2. Although the mean molecular gas mass (5 × 10(10) solar masses) of the submillimetre bright galaxies can explain the formation of typical elliptical galaxies, it is inadequate to form elliptical galaxies that already have stellar masses above 2 × 10(11) solar masses at z ≈ 2. Here we report multi-wavelength high-resolution observations of a rare merger of two massive submillimetre bright galaxies at z = 2.3. The system is seen to be forming stars at a rate of 2,000 solar masses per year. The star-formation efficiency is an order of magnitude greater than that of normal galaxies, so the gas reservoir will be exhausted and star formation will be quenched in only around 200 million years. At a projected separation of 19 kiloparsecs, the two massive starbursts are about to merge and form a passive elliptical galaxy with a stellar mass of about 4 × 10(11) solar masses. We conclude that gas-rich major galaxy mergers with intense star formation can form the most massive elliptical galaxies by z ≈ 1.5.

Increased blood volume and CD34(+)CD38(-) progenitor cell recovery using a novel umbilical cord blood collection system.

A major problem with the use of umbilical cord/placental blood (UCB) is the limited blood volume that can be collected from a single donor. In this study, we evaluated a novel system for the collection of UCB and analyzed the kinetics of output of hematopoietic stem cells in the collected blood. Sequential UCB fractions were collected from 48 placentas by gravity following common procedures. When UCB flow was ended, collection was continued using the device. Nucleated cell (NC) density in each fraction was evaluated and the expression of CD34, CD38 and other hematopoietic markers was assessed by flow cytometry. The total collected volume was 60.9 +/- 26.2 ml (mean +/- SD, range 17-141.5). The device yield (volume collected using the device/total volume) was 26.5 +/- 15.1%. No significant difference was observed in NC count in sequential fractions. A significant increase in CD34(+) cell content in sequential fractions and a 2.07 +/- 1.18-fold increase in the percentage of CD34(+) cells in the last versus first fraction were observed. Furthermore, within the CD34(+) population, the percentage of CD38(-) pluripotent stem cells in the first fraction was 3.24 +/- 1.39, while in the last fraction it raised to 34.43 +/- 22.62. Thus, at the end of a collection performed following current procedures, further blood rich in the most primitive progenitor cells can be recovered. Therefore, the optimization and standardization of collection procedures are required to obtain maximal recovery from each placenta and increase the percentage of UCB units suitable for clinical use.

Phenotypic characterization of immunomagnetically purified umbilical cord blood CD34+ cells.

This study describes the multilineage differentiation pattern of purified CD34+ stem cells obtained from human umbilical cord blood. CD34+ cells were collected from 49 umbilical cord blood samples. Following immunomagnetic purification, cells were double stained with anti CD34 and CD71, CD61, CD7, CD19, CD33, CD36 and triple stained with anti CD34, CD38 and HLA-DR. Analysis were performed using a FACScan flow cytometer. After purification, the mean CD34+ cells' purity was 85.49 +/- 7.08%. Several subpopulations of umbilical cord blood CD34+ cells were identified indicating different lineage commitment. The majority of CD34+ cells expressed both CD38 and HLA-DR (91.74 +/- 3.76%), while those lacking CD38 were 3.43 +/- 2.12% (CD38-DR+) and 1.81 +/- 1.54% (CD38-DR-). These data were compared to the expression of lineage commitment markers on purified CD34+ cells from 5 mobilized peripheral blood samples. The percentage of peripheral blood CD34+CD38-DR+) and CD34+CD38-DR- cells was significantly lower than umbilical cord blood, 0.24 +/- 0.18% and 0.04 +/- 0.03% respectively. The knowledge and standardized of umbilical cord blood CD34+ cells phenotype is critical since umbilical cord blood volume is limited. The homogeneity of CD34+ subpopulation phenotype suggests that monitoring of lineage differentiation antigens may not be relevant for clinical use of umbilical cord blood samples. However, the observed higher percentage of pluripotent CD34+38- stem cells in umbilical cord blood compared to peripheral blood, that might explain the successful clinical use of umbilical cord blood even when low number of cells are used, candidates these antigens as the predictive parameter for clinical use of umbilical cord blood samples.

Age-related persistent clonal expansions of CD28(-) cells: phenotypic and molecular TCR analysis reveals both CD4(+) and CD4(+)CD8(+) cells with identical CDR3 sequences.

In a small group of subjects we had identified persistent expansions (range 6-72%) of CD4(+)CD8(+) double-positive (DP) peripheral blood (PB) cells which express the CD8 alpha/alpha homodimer. Here, DP cells present in a larger cohort were further investigated and found by FACS analysis to express a single or a dominant TCRBV family. In these subjects, with a mean age of about 64 years, expansions of CD4(+) cells with the same TCRBV family specificity as in the respective DP cells also were consistently detected. TCR heterogeneity of the dominant TCRBV family was specifically evaluated: The amplified CDR3 region was cloned and found to consist of one single or two largely dominant sequence patterns. Furthermore, cloning of the CDR3 region from FACS-sorted DP, CD4(+), or CD8(+) cells indicates that both DP and CD4(+), but not CD8(+) cells, isolated from the same individual possess a striking identity of the CDR3 regions. As indicated by FACS analysis, the clonally expanded cells occur in the CD4(+)CD28(-) cells. Taken together, these results suggest that expanded CD4(+)CD28(-) cells might also acquire CD8 alpha/alpha expression and become DP and imply that CD4 clonality is a more frequent phenomenon than previously suspected. In conclusion, the persistent expansions described in this report represent a novel group of age-related benign clonal expansions of still undefined significance of a rare CD28(-) T cell subset.

Effect of marrow processing on hematopoietic cell recovery in bone marrow harvests: focus on filtration.

Bone marrow processing requires a first step of filtration to remove small clots, bone fragments, fat cells and fibrin followed by centrifugation to separate mononuclear cells (MNC). These procedures cause a significant loss of cells potentially including hematopoietic stem cells (HSC). We therefore analyzed the cell recovery and phenotype of various fractions (whole marrow; filtered marrow; MNC collected after centrifugation; bone marrow fragments trapped by filtration) of bone marrow harvests (BMH) from patients with different hematological malignancies undergoing autologous bone marrow transplantation. Analysis of 25 BMH showed that the mean percentage of WBC and MNC recovered after filtration was respectively 92.28 +/- 7.42% and 92.3 +/- 9.05% of the original BMH while after centrifugation the percentage was 20.23 +/- 6.47% and 75.7 +/- 12.81%. The percentage of cells present in the tissue fragments trapped in the filters obtained from five BMH was only 3.93 +/- 1.25% (WBC) and 5.65 +/- 2.2% (MNC) of those originally present in the harvest. Phenotypic analysis performed on the same samples showed that there is no selective loss of MNC or CD34+ cells in the filtration process. Our data indicate that processing of BMH, in particular filtration of tissue fragments, does not affect the recovery of HSC.

[Autogenic training versus Erickson's analogical technique in treatment of fibromyalgia syndrome]. / Training autogeno versus tecniche analogiche ericksoniane nella terapia della sindrome fibromialgica.

The AA have conducted a controlled trial to determine the efficacy of two verbal techniques for muscular relaxation on 53 patients with fibromyalgia. The subjects were assigned at random to a autogenous training group (27 patients) or a analogic Erickson's techniques group (26 patients). The autogenous training showed the presence of various limits: (1) application limits (in which notable difficulties had to be faced to train the patients with fibromyalgia to practice the Autogenous training due to the revelation of "intrusive thoughts" or "abreactions", or because of the incapacity of the patients to practice the exercises at home without hearing the instructions of a therapist); (2) limits of efficacy (the state of optimum training needed many therapeutic sittings in order to be achieved and the improvements regarded nighttime sleep and morning rigidity, however, these improvements were less than those obtained with the analogic Erickson's techniques). The Erickson's techniques have showed, instead, many advantages: numerous patients continued the treatment until it was finished; only a small number of therapeutic sittings were necessary. There was an improvement of all the parameters examined, superior compared to the results obtained in the group of patients treated with autogenous training.

Phenotypic heterogeneity of persistent expansions of CD4+ CD8+ T cells.

A group of 18 individuals is described that manifest persistent (follow up between 4 and 57 months) expansions (ranging from 10 to 70%) of CD4+ CD8+ peripheral T cells. In nine individuals there was no apparent underlying disease whereas the remaining displayed a wide range of unrelated diseases. Analysis of the cell surface immunophenotype showed that all individuals express high densities of CD2, CD3, CD5, and TCR alpha/beta on their CD4+ CD8+ subset. On the contrary, these cells did not express CD25, CD38, CD71, HLA-DR, and the beta chain of the interleukin-2 receptor (p75) but expressed high density of CD29 and low density or absence of CD7. CD8 was "dim" in most individuals and consisted only of the CD8 alpha chain isoform. These individuals could be further divided into two subgroups based on the following parameters: in eleven cases CD4+ CD8+ cells had an LGL morphology and expressed the CD11b, CD56 and CD57 NK-associated antigens; in addition, a high percentage of CD4+ CD8- cells from the same individuals also expressed NK-associated antigens on their cell surface (subgroup A). The CD4+ CD8+ cells of the remaining individuals had small lymphocyte morphology, expressed little or no CD11b and CD56 and their CD4+ CD8- cells did not express NK-associated antigens at all (subgroup B). Finally, CD8 was "bright" on the CD4+ CD8+ cells of three individuals and in these cells also the CD8 beta chain isoform was present (subgroup C). Southern blot hybridization of genomic DNA with a T-cell receptor beta probe revealed that of the sixteen individuals examined four had a monoclonal, seven an oligoclonal, and five a polyclonal molecular configuration. The present data indicate that persistent CD4+ CD8+ expansions represent a novel heterogeneous subset of T cells.

Persistent expansions of CD4+ CD8+ peripheral blood T cells.

CD4+ CD8+ cells are present during T cell differentiation in the thymus. Less than 2% of normal T cells that coexpress CD4 and CD8 also are released in the circulation and are present in the peripheral blood. In this study, nine individuals are described that manifested persistent expansions (11% to 43%) of circulating CD4+ CD8+ T cells that in three cases had large granular lymphocyte (LGL) morphology in the absence of either lymphocytosis or overt lymphoproliferative disorders. Southern blot hybridization of enriched CD4+ CD8+ cells with T-cell receptor beta (TCR beta) and TCR gamma probes showed that most cases had the 12-kb Eco RI germinal band deleted or of decreased intensity. In several individuals new TCR beta-specific bands of different intensity and distinct from case to case suggested either monoclonal or oligoclonal and polyclonal expansions. Immunophenotypic analysis showed that in 7 out of 9 cases the CD4+ CD8+ T cells presented with CD8 dim expression. Furthermore, all the CD4+ CD8+ cells did not express many of the known activation antigens (low or absent CD25, CD38, CD71, HLA-DR), whereas they expressed high levels of CD2, CD29, CD56, and CD57. In addition, the CD4+ CD8+ cells of 5 out of 9 subjects coexpressed CD45RA and CD45RO suggesting that these cells might be "frozen" in an intermediate state between naive and memory T cells. In conclusion, the present CD4+ CD8+ cases fall within a larger spectrum of disorders ranging from apparently normal to reactive or proliferative situations and encompassing cells with LGL morphology or LGL-associated antigens expression either in the presence or in the absence of absolute lymphocytosis that deserve careful follow-up investigations.

Cytotoxic in vitro function in patients with metastatic renal cell carcinoma before and after alpha-2b-interferon therapy. Effects of activation with recombinant interleukin-2.

In this study the characteristics of the cytotoxic function in a series of patients with metastatic renal cell carcinoma (RCC) were analyzed and the possibility of modulating this capacity in vitro with the use of biologic response modifiers (BMR) such as alpha-interferon (alpha-IFN) and recombinant interleukin-2 (rIL-2) was verified, with the ultimate goal of providing a rationale for a therapeutic approach to this disease with these molecules. Peripheral blood mononuclear cells (PBMC) of patients with advanced RCC were tested for natural killer (NK) and lymphokine-activated killer (LAK) activity both before and after alpha-IFN therapy. In addition, surface markers of unstimulated and stimulated cells were analyzed and in vitro assays were performed to determine the proliferative capacity in response to the stimulus with rIL-2. During an evaluation before treatment, defective NK activity was observed that could be corrected by incubating the cells with rIL-2. In these subjects, LAK cells could be consistently generated after PBMC were activated with this cytokine in vitro. No changes in NK and LAK activity were found after alpha-IFN therapy. In contrast, treatment with alpha-IFN affected the proliferative response of PBMC to rIL-2, and a significant decrease in this in vitro capacity was observed during follow-up. The ability to restore NK activity and obtain an adequate LAK cytotoxicity from the PBMC of patients with RCC supports a therapeutic approach with BRM. However, the fact that this type of treatment affects the proliferative response of PBMC to rIL-2 must be considered when clinical trials are designed for patients with RCC.

Different mechanisms of activation of proliferating CD3+ cells in patients with lymphoproliferative disease of granular lymphocytes.

To investigate the role of p55 and p75 chains of interleukin-2 receptor (IL-2R) on the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), the cells obtained from 11 LDGL patients (belonging to the CD3+ group) were studied for (a) the surface expression and (b) mRNA transcripts of the p55 and p75 IL-2R after activation with anti-CD3 monoclonal antibody (mAb) or interleukin-2 (IL-2). The effects of mAbs specifically blocking the p55 and p75 IL-2R on the generation of proliferative and cytotoxic functions were studied following anti-CD3 mAb stimulation. A significant difference was observed in the expression of p55 and p75 antigens on LDGL cells under resting conditions: a low number of p55 IL-2R+ (mean 1.2 +/- 0.4%) and high values of p75 IL-2R+ cells (54.9 +/- 7.4%). Accordingly, a barely detectable message for the p55 IL-2R and a strong signal for the p75 IL-2R mRNA were demonstrated. Following activation with anti-CD3 or IL-2, different patterns of IL-2R expression were observed. Anti-CD3 mAb induced an increase in the expression of the p55 IL-2R both at the mRNA and antigen level, whereas the p75 values remained consistently raised. In contrast, IL-2 induced the expression of p55 IL-2R mRNA associated with only a slight expression of this antigen. This finding was associated with a decrease in the cell expression of the p75 IL-2R, whereas the amount of p75 mRNA was unchanged. Both anti-CD3 mAb and IL-2 induced cell proliferation and cytotoxicity against the K-562 target cells. Anti-p55 IL-2R mAb did not affect the cytotoxic activity mediated by anti-CD3, but it markedly inhibited cell proliferation. Anti-p75 mAb did not inhibit either lytic function or cell proliferation mediated by anti-CD3 mAb, suggesting that only the high affinity IL-2R (p55 plus p75) is involved in anti-CD3 mediated cell activation in LDGL patients. This mechanism is different from that responsible for the IL-2 activation of CD3+ GL in LDGL patients, which is achieved through the p75 IL-2R alone. These results provide new insights into the pathophysiology of proliferating GL in LDGL patients and may also contribute to further characterization of the normal CD3+ GL population.

Tumor necrosis factor-alpha and B-cell growth factor induce leukemic hairy cells to proliferate in vitro.

To clarify the mechanisms accounting for the hairy cell proliferation, in five patients with hairy cell leukemia (HCL), we evaluated the ability of neoplastic cells to proliferate in vitro in response to tumor necrosis factor-alpha (TNF-alpha), B-cell growth factor (BCGF), and interleukin 4 (IL-4). In addition, supernatants recovered from cultures of unstimulated hairy cells were tested for the capability to induce the proliferation of allogeneic hairy cells. We demonstrated that TNF-alpha and BCGF were able to induce the in vitro growth of hairy cells (stimulation index (SI) ranging, at different concentrations, from 1.6 to 10.7 and from 1.6 to 25.1 for TNF-alpha and BCGF, respectively). IL-4 did not show any proliferative effect on hairy cells. When unstimulated hairy cell supernatants were tested for the proliferative activity on allogeneic hairy cells, we demonstrated a low proliferative effect that was not inhibited by an anti-TNF-alpha antibody. Our findings demonstrate that unstimulated hairy cells proliferate in vitro in response to TNF-alpha and BCGF, thus suggesting that these cytokines could be involved in an autocrine model of cell proliferation.

Cell membrane expression and functional role of the p75 subunit of interleukin-2 receptor in lymphoproliferative disease of granular lymphocytes.

The cell membrane expression and functional role of the interleukin-2 receptor (IL-2R) was analyzed in nine patients with lymphoproliferative disease of granular lymphocytes (LDGL) using monoclonal antibodies (MoAbs) specific for the p75 (TU27) and the p55 (anti-Tac) subunits of IL-2R. Four patients were characterized by the proliferation of CD3+CD8+ granular lymphocytes (GL) expressing the alpha/beta T-cell receptor (T alpha beta) and one case by the proliferation of CD3+CD4-CD8- GL expressing the gamma/delta T-cell receptor (T gamma delta); in four additional cases proliferating cells were CD3 negative GL. Consistent with data observed on normal GL, phenotypic analysis demonstrated that patients' GL lack the expression of the p55 IL-2R, whereas the p75 subunit is constitutionally expressed by expanding GL of both T-cell (either T alpha beta and T gamma delta) and natural killer (NK) origin in variable proportions (11% to 94% of cells). The analysis of the cytotoxic and proliferative activity demonstrated that the anti-p55 MoAb failed to inhibit IL-2-mediated activation, whereas a marked inhibition of both cytotoxicity and proliferation were obtained using the anti-p75 chain specific MoAb. These data indicate that the p75 chain of IL-2R is responsible for IL-2 signal transduction in both CD3+ and CD3- LDGL patients' GL.

Mechanisms accounting for lymphocytic alveolitis in hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is a lung disorder characterized by an exaggerated accumulation of CD8+ T lymphocytes in the pulmonary parenchyma. To investigate the mechanisms accounting for the T cell alveolitis taking place in the lung of HP patients and their pattern of growth, cells recovered from the bronchoalveolar lavage (BAL) of seven patients were evaluated for: 1) the expression of activation markers, including IL-2R (p55 and p75 subunits), HLA-DR and VLA-1 Ag; 2) the ability of IL-2 and IL-4 to induce in vitro proliferation; 3) the capability to synthesize and release IL-2 by determining the levels of IL-2 in BAL cell-free supernatants and by evaluating the presence of mRNA transcripts for IL-2; and 4) the molecular configuration of the beta- and gamma-genes of the TCR. This study demonstrates that a high number of BAL lymphocytes recovered from the lungs of HP patients express activation markers including the p75 chain of IL-2R, VLA-1, and HLA-DR Ag. These cells express the CD3+,CD8+,CD16-,CD56+ phenotype and proliferate in vitro in the presence of IL-2 but do not release this cytokine. Furthermore, IL-2 transcripts could not be detected in BAL resting T lymphocytes. No proliferation was observed in the presence of IL-4. The analysis of the configuration of the TCR beta- and gamma-genes showed a polyclonal pattern, with the exception of one case in which extra bands were observed following digestion with BamHI and EcoRI restriction enzymes. Taken together, our data suggest that the IL-2 system may play a central role in the mechanisms accounting for lymphocytic alveolitis in HP patients. Although the pattern of growth is usually polyclonal, such polyclonal recruitment seems to be biased toward cells that have rearranged and possibly expressed particular V beta or V gamma genes, thus leading to the hypothesis that the events that take place in the lung of these patients may occasionally elicit an oligoclonal expansion of the cells proliferating in lung parenchyma.

Cytotoxic events taking place in the lung of patients with HIV-1 infection. Evidence of an intrinsic defect of the major histocompatibility complex-unrestricted killing partially restored by the incubation with rIL-2.

To characterize the cytotoxic events taking place in the lung of patients with HIV-1 infection, we studied the cells recovered from the bronchoalveolar lavage (BAL) of nine patients with AIDS, seven patients with AIDS-related complex, and two patients with lymphadenopathy. Phenotypic analysis was coupled to a series of functional evaluations of nonspecific cytotoxic abilities performed on lung effectors, including their property to bind K-562 targets, to release natural killer cytotoxic factor (NKCF), and to become cytotoxic following in vitro activation with rIL-2. Our results demonstrated that lung cells bearing the NK-related CD16, CD56, and CD57 antigens were quantitatively increased, irrespective of the disease stage. The majority of the cells also coexpressed the CD3 molecule and the alpha/beta T cell receptor (TCR), notably the phenotype characterizing MHC-unrestricted cytotoxic T cells. From a functional point of view, a severe impairment of the spontaneous cytotoxic ability was demonstrated in most patients. Evaluation at the single cell level showed a normal percentage of the effector/target conjugates formed by HIV-1 lymphocytes. The release of NKCF was undetectable in patients with AIDS even following lectin stimulation, whereas BAL cells from patients with earlier infection produced and/or could be triggered to release discrete amounts of NKCF by incubation with PHA. Studies designed to activate lung cytotoxic cells with rIL-2 showed that in most patients the stimulation of effector cells with rIL-2 enhanced the spontaneous killing and elicited a lymphokine-activated killer (LAK) phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of renal carcinoma with alpha-interferon: biological bases and clinical results]. / II trattamento del carcinoma renale con alpha-interferon: basi biologiche e risultati clinici.

The distinctive biology of renal cell carcinoma and its low response to conventional therapies have prompted researchers in this field to search for other therapeutic strategies. In this paper we describe the current concepts regarding the biology of this neoplasia and new therapeutic perspectives for this disorder, with particular interest in the use of biological response modifiers, including alpha-interferon (alpha-IFN). In view of the evidence of spontaneous regressions of metastases observed after nephrectomy, a possible role of the immune system has been hypothesized in modulating the natural course of renal cell carcinoma. In this context, several groups have focused their attention on the immunotherapeutic approach to this disease. Major biological characteristics of alpha-IFN are reported here, with particular attention paid to its immunomodulatory properties. As a matter of fact, significant results have been obtained by using this molecule, either alone or in association with chemotherapeutic agents (vinblastine). In this paper we focus on the efficacy of these therapeutic approaches by reporting the data obtained from the major clinical trials in which alpha-IFN has been used, including a personal series of cases.

Susceptibility to lysis of pulmonary alveolar macrophages by human lymphokine-activated killer cells.

In this study we addressed the question of whether lymphokine-activated killer (LAK) cells, besides killing neoplastic cells, may exert a certain degree of lysis on the normal counterpart; in particular we took into consideration the toxicity against pulmonary alveolar macrophages (PAM). We demonstrated that human LAK cells generated in vitro following incubation of peripheral blood mononuclear cells with recombinant interleukin 2 for 4 days were able to lyse normal PAM in a 4-h 51Cr release assay. Similarly, PAM recovered from patients suffering from nonneoplastic interstitial lung disorders, i.e., sarcoidosis and hypersensitivity pneumonitis, were shown to be susceptible to the cytotoxic function provided by LAK cells. Both autologous and allogeneic PAM were lysed by LAK cells, thus suggesting that the phenomenon we observed does not require a major histocompatibility complex restriction. Preincubation of PAM under study with gamma-interferon did not affect their susceptibility to the lysis mediated by LAK cells. Furthermore, cold target inhibition assay demonstrated that normal PAM could efficiently compete with both NK-sensitive and NK-resistant target lines for the binding sites on LAK cells, thus indicating that the putative receptor(s), or at least the mechanism of target recognition, is shared by PAM and these different target cell lines. The evidence herein provided that LAK cells are cytotoxic to normal, nontransformed PAM points out that the pathogenetic mechanisms involving this self-addressed lytic activity could account for some adverse reactions related to LAK/interleukin 2 immunotherapy.

Bronchoalveolar lavage and the immunology of lung cancer.

Current concepts on the application of bronchoalveolar lavage (BAL) for the investigation of tumor markers and antitumor activities exerted by effector cells in the lung parenchyma are summarized. The evaluation of BAL cellular and humoral constituents might provide new insights into the pathogenic mechanisms taking place in lung cancer.