Immunocompetence in lung cancer patients: analysis of serological and cellular parameters.

Some serological (serum immunoglobulins, circulating immune complexes, quantitative assessment of hemolytic complement activity) and cellular (total number of circulating lymphocytes as well their phenotypic and functional characterization) parameters have been analyzed in 42 patients with lung cancer of three hystologic types and in 19 healthy controls to define whether different histologic neoplasms have an impact on the host immune system. As a group, cancer patients showed 1) the presence of circulating immune complexes, in a significant percentage, within all the three groups studied; and 2) a significant reduction of lymphocytes forming E rosette. With regard to cellular immune parameters we noted that 1) T lymphocytes isolated from the peripheral blood lymphocytes (PBL) of patients with lung cancer showed a decreased capacity to express HLA-class II antigens upon phytohemogglutinin (PHA) activation in vitro; 2) PBL from lung cancer, in particular the adenocarcinoma group, failed to proliferate upon stimulation by policlonal mitogens; and 3) the autologous mixed lymphocyte reaction (MLR) of non-T/T-type was impaired in all three groups, whereas the autologous MLR of T/T-type was impaired only in the patients with squamous cell carcinoma and in those with adenocarcinoma, probably as a result of a reduced stimulatory capacity.

Plasmaexchange plus immunoglobulins for treatment of hypergammaglobulinaemic patients with AIDS and AIDS-related complex (ARC).

AIDS patients often develop a conspicuous although functionally ineffective hypergammaglobulinaemia. We have treated four patients affected by AIDS or AIDS-related complex (ARC) with repeated courses of plasmaexchange coupled with immunoglobulin infusions. The schedule of each course was as follows: one plasmapheresis treatment once a week for 5 consecutive weeks, each treatment amounting to an average exchange of 3000 ml of plasma, replaced by plasma/protein and 5% albumin/physiological saline solutions, and followed by infusion of 15 gr of human immunoglobulins. Each plasmapheresis course was completed by additional weekly administrations of the same amount of human immunoglobulins. In each patient we noted fast cessation of fever, weight gain, and an overall clinical amelioration with decrease of infections, asthenia, and anorexia. Haematological, serological, and immunological parameters (particularly IgG serum levels) also significantly improved after treatment.

Deficiency of the autologous mixed lymphocyte reactions of non-T/T and T/T type in intravenous drug abusers infected by the human immunodeficiency virus (HIV).

In the present study both responsiveness and stimulatory capacity in autologous mixed lymphocyte reactions (AMLRs) of non-T/T and T/T type, as well as in allogeneic mixed lymphocyte reaction (MLR), were evaluated in 30 intravenous drug abusers (IDAs) infected by the human immunodeficiency virus (HIV) and in 10 HIV-negative IDAs. The production of interleukin 2 (IL2), and the expression of HLA Class II antigens and IL2 receptors by PHA-activated T lymphocytes were also evaluated. A severe impairment of both responsiveness and stimulatory capacity in MLR and AMLRs was found in the HIV-positive IDAs and not in the HIV-negative IDAs. The HIV-positive IDAs showed also a defective expression of HLA Class II antigens, whereas the IL2 production and the IL2 receptor expression were in the normal range. The present data are consistent with similar observations in male homosexuals with AIDS-related complex and confirm that the HIV infection induces a broad spectrum of immunological abnormalities leading to a progressive derangement of the immunocompetence.

Abnormalities of T cells isolated from mediastinal lymph nodes and peripheral blood of patients with lung carcinoma: deficit in PHA-induced expression of HLA class II antigens and in autologous mixed lymphocyte reactions.

A reduced percentage of T cells isolated from mediastinal lymph nodes and peripheral blood of patients with lung carcinoma acquired HLA Class II antigens following in vitro stimulation with PHA. Furthermore T cells were functionally abnormal in autologous and allogeneic mixed lymphocyte reactions (MLR). The immunoregulatory properties of HLA Class II antigens and autologous MLRs suggest that these abnormalities may affect the interaction of the host's immune system with tumor cells.

Circadian variations of autologous mixed lymphocyte reactions and endogenous cortisol.

The degree of proliferation of human T cells stimulated with autologous PHA-T cells and with autologous non-T cells displays circadian variations. The highest proliferation occurs with cells isolated from blood drawn at 8 a.m. in mixed lymphocyte reactions (MLR) with autologous PHA-T cells and from blood drawn at 8 p.m. in MLR with autologous non-T cells. The circadian variations of autologous MLRs appear to reflect changes in the proliferative response of T cells. In autologous MLRs with non-T cells as stimulators the extent of proliferation was inversely correlated with the level of endogenous cortisol. The circadian variations of autologous MLRs do not reflect non-specific changes in the proliferative and stimulatory properties of T and non-T cells, since circadian variations were not observed in the proliferative response of T cells to mitogens and in allogeneic MLRs. Circadian variations of autologous MLRs must be taken into account when analyzing abnormalities of these reactions in pathological conditions.

T-lymphocytes phenotype and functions in patients with head and neck cancer.

We studied the phenotype of T-lymphocytes isolated from 18 patients with head and neck cancer, their capacity to express Ia antigens upon activation by lectins in vitro, their capacity to function either as responder or stimulator cells in autologous mixed lymphocyte reaction, and their capacity to cooperate with the normal adherent suppressor cells (NASC). The T-lymphocytes isolated from these patients have several functional defects including an impaired capacity to activate allogeneic lymphocytes in mixed lymphocyte reactions (MLRs), a lack of a proliferative capacity in autologous MLRs, an impaired sensitivity to inhibition by NASC, and an impaired capacity to express Ia antigens upon activation by mitogens in vitro. These data indicate that, in patients with head and neck cancer, immune function is characterized by a defect in T-lymphocytes functions which concerns the process of cell to cell cooperation.

Lymphocytapheresis in the treatment of rheumatoid arthritis: clinical and immunological studies.

Six patients with Rheumatoid Arthritis (RA) have been treated with lymphocytapheresis after their disease proved unresponsive to conventional therapy. Clinical improvement, measured evaluating articular swelling, morning stiffness, and muscle weakness, was observed in four of the six patients. From the cellular point of view lymphocytapheresis induced (1) T cell depletion without modification of lymphocyte subsets in the peripheral blood, (2) improvement of lymphocyte responsiveness to lectins, autoantigens and alloantigens. All together these data suggest that therapeutic leukapheresis modifies the immune responsiveness in humans, possibly facilitating the process of cell to cell cooperation.

Role of normal adherent cells in the regulation of the autologous mixed lymphocyte reactions in humans.

The effect of normal adherent suppressor cells on the blastogenesis of human T lymphocytes in the mixed lymphocyte reaction (MLR) was studied in both allogeneic and autologous combinations. Non-T cells and Ia+ T lymphocytes were used as stimulator cells in both allogeneic and autologous MLR. The addition of adherent cells to the stimulators inhibited blastogenesis of T lymphocytes in both types of MLR when the stimulator population was made up of non-T lymphocytes but did not interfere with blastogenesis when Ia+ T lymphocytes were used as stimulator cells. The present data indicate that the T lymphocytes able to respond to Ia+ T cells (in the MLR, autologous or allogeneic) may be different from those which respond to non-T lymphocytes or may be less sensitive to the regulatory function of normal adherent cells.

Decreased sensitivity of T lymphocytes to normal adherent suppressor cells in patients with head and neck cancer.

The sensitivity of T Lymphocytes to the inhibitory action of normal adherent cells in the mixed lymphocyte reaction (MLR) was studied in 20 subjects with head and neck cancer. T lymphocytes from cancer patients proliferated in the MLR both in the absence and in the presence of increasing numbers of autologous as well as allogeneic adherent cells, while the blastogenesis of T lymphocytes from controls was inhibited up to 70% by the addition of adherent cells to the culture. Such a lack of sensitivity to adherent cells in cancer patients occurred both in allogeneic and in autologous MLR. These observations indicate that the immunocompetence of patients with head and neck cancer may be related to a defect of macrophage-T lymphocyte interaction similar to the one described in patients with common varied immunodeficiency.