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PURPOSE: Although the accumulation of CD4 cells in the lung and other involved tissues is regarded as the distinctive immunologic feature of sarcoidesis, a few sarcoid patients can present with CD8 alveolitis. This study evaluates the incidence as well as the clinical and immunologic features of sarcoidosis presenting with CD8 alveolitis. PATS AND METHODS: A total of 2,214 consecutive bronchoalveolar lavuge (BAL) spocimens obtained from 481 patients with sarcoidesis between January 1985 and December 1991 were retrospectively analyzed. Subjects who entered the study had the following characteristics: (1) lymphocyte alveolitis and (2) lung CD4/CD8 ratio less than 1.0. Only data obtained from patients with a first episode of pulmonary involvement were included in the analysis (394 patients). RESULTS: Fifteen of the 394 patients studied at the time of diagnosis showed CD8 alveolitis as the presenting manifestation; the incidence of this phenomenon was 3.8 %. A follow-up study of BAL T-cell subsets demonstrated that patients who showed high-intensity CD8 alveolitis at the onset of the disease maintained the CD8 pattern of alveolitis during relapses. Phenotypic analysis of lung T cells revealed that the accumulation of CD8 lymphocytes was due to the discrete local increase of CD45RO+ 'memory' cells equipped with a number of accessory structures, including adhesion molecules and class II major histocompatibility complex-related HLA-DR antigen. CONCLUSIONS: The accumulation of CD8 cells in the sarcoid lung is likely to reflect a homing of memory cells due to the ongoing immunologic response against the unknown antigen cansing the disease. Although CD8 alveolitis can be considered a relatively rare event in sarcoidesis, the possibility that an increase of CD8 cells in the BAL fluid might be sustained by an underlying sarcoid inflammatory process should never be dismissed on clinical grounds in patients with interstitial lung disease.

No one knows exactly why it is possible to easily isolate various infecting agents such as Pneumocystis carinii, as well as other opportunistic and nonopportunistic agents, from the lungs of patients infected with human immunodeficiency virus, type 1 (HIV-1). Moreover, patients with acquired immunodeficiency syndrome (AIDS) are more susceptible to noninfectious disorders of the lung. It may be that HIV-1 infection affects the ability of the immunocompetent cells of the lungs to defend themselves. Certain cells in the lungs, called natural killer (NK) cells, are increased in number in patients with HIV-1, but they are functionally inactive. This study was done to find out more about the cell-killing (cytotoxic) events that take place in the lungs of patients with HIV-1 infections. Cells were studied that had been washed from the lungs of nine patients with AIDS, seven other patients with AIDS-related complex, and two patients with lymphadenopathy (disease of the lymph nodes). As a result of the study, evidence is provided that patients with HIV-1 infection have pulmonary cells that interact with targets, but fail to kill them because the cells did not release natural killer cytotoxic factor. Certain biologic response modifiers are able to restore cell function in the test tube (in vitro), and may help in designing new strategies for treating AIDS-associated pulmonary complications. (Consumer Summary produced by Reliance Medical Information, Inc.)

In the current study, we investigated the cytotoxi ability of peripheral blood mononuclear cells (PBMC) recovered from patients with acute nonlymphoblastic leukemia (ANLL) in complete remission (CR) against natural killer (NK)-sensitive, NK-resistant, autologous and allogeneic leukemic target cells taken at diagnosis. Our purpose was to define the role played by cytotoxic mechanisms in the control of leukemia cell growth in ANLL. Experiments were carried out at resting conditions and after in vitro activation with recombinant interleukin-2 (rIL-2) and anti-CD3 monoclonal antibody (moAb). At resting conditions, PBMC recovered from ANLL patients displayed a NK function that was not significantly different from controls (mean [plus or minus] standard error of the mean [SEM]: 21.9% [plus or minus] 3.9% versus control values of 27.5% [plus or minus] 2.9%; the P value was not significant [NSD]), but they were unable to show cytotoxic activity against autologous and allogeneic leukemia cells. After in vitro boosting with rIL-2, PBMC were able to generate lymphokine activated killer (LAK) cells, as demonstrated by an increased killing of NK-resistant Daudi targets (16.3% [+ or -] 2.7%). Although LAK activity was quantitatively lower than in control subjects (mean [plus or minus] SEM: 16.3% [+ or -] 2.7% versus control values of 7.8% [plus or minus] 3.1%; P < 0.001), it still exerted a cytotoxic effect against autologous and allogeneic leukemic cells. Similar results were obtained when anti-CD3 moAb was used as a stimulus in vitro. Our data suggest that nonspecific cytotoxic cells may be triggered to exert an in vitro cytotoxic effect on leukemic cells, which could possibly play a key role in vivo in the control of leukemic cell growth regulation. Cancer 64-667-672, 1989.

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 α/βT-cell receptor (Tαβ) and one case by the proliferation of CD3+CD4–CD8– GL expressing the γ/δ T-cell receptor (Tγδ); 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 Tαβand Tγδ) 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.