Lymphocyte proliferation to artery antigen as a positive diagnostic test in polymyalgia rheumatica.

The transformation response of peripheral blood lymphocytes in vitro to human arterial and muscle antigen has been studied in patients with polymyalgia rheumatica, polymyositis, rheumatoid arthritis, and polyarteritis, and polyarteritis nodosa and in unrelated controls. Lymphocytes from patients with polymyalgia rheumatica showed transformation responses significantly higher to artery antigen than those in the other disease and control groups. The highest responses were found in patients with evidence of the most active clinical disease at the time of testing.

Experimental myositis in rats. II. The sensitivity of spleen cells to syngeneic muscle antigen.

The transformation responses to a syngeneic muscle homogenate of spleen cells, lymph node cells and blood lymphocytes have been studied in rats with allergic myositis. Significantly increased responses to muscle were obtained only for spleen cells from rats which had received two or more immunizing injections of heterologous muscle with Freund's complete adjuvant. Other populations of lymphoid cells which had previously been shown to be capable of transferring the disease did not show significant transformation responses to muscle.

Lymphocyte reactivity in pregnant women and newborn infants.

The mitotic response to phytohaemagglutinin (PHA) was determined in lymphocytes of mothers and their newborn infants obtained at delivery and seven days later by measuring the rate of 125 I-idoxuridine uptake into DNA in lymphocytes cultured in their own plasma and after washing and resuspension in fetal bovine serum. There was no difference in the unstimulated counts of maternal lymphocytes taken at delivery, whether unwashed or washed, compared with those from nonpregnant controls. With PHA stimulation the mitotic response of the maternal lymphocytes cultured in their own plasma was reduced compared with that of the control lymphocytes but washed maternal cells showed a similar response to the controls.

The cytotoxic activity of lymphocytes from human lymph in vitro.

The cytotoxicity and DNA synthesis of thoracic duct and blood lymphocytes from four patients have been studied on the 1st day of drainage. Three patients were being drained as a pretreatment for kidney transplantation and one had myasthenia gravis. In one patient lymphocytes were obtained from a lymphatic fistula in the groin and from the blood 5 weeks after drainage began.

Experimental myositis in rats. I. Histological and creatine phosphokinase changes, and passive transfer to normal syngeneic rats.

An allergic myositis was produced in an inbred strain of rats by giving repeated injections of heterologous muscle with complete Freund's adjuvant. Histological lesions developed after two or more injections. The activity in the serum of the enzyme creatine phosphokinase (CPK) was found to be elevated after two injections and reached maximum levels after three to six injections.

Immunosuppression in the treatment of inflammatory bowel disease. I. Changes in lymphoid sub-populations in the blood and rectal mucosa following cessation of treatment with azathioprine.

Lymphoid subpopulations in the blood and rectal mucosa were studied in six patients with ulcerative colitis or Crohn's disease who had been treated for over three years with azathioprine. Serial assays were performed to observe the changes occurring up to 12 weeks after treatment with azathioprine was stopped. While the patients were on the drug two lymphoid populations showed marked depression.

Effector activating determinants on IgG. II. Differentiation of the combining sites for C1q from those for cytotoxic K cells and neutrophils by plasmin digestion of rabbits IgG.

Plasmin digestion of rabbit IgG after pretreatment at low pH yields a fragment (Facb) which has lost the C3 domain. A study of the biological activity of this fragment is described and the following conclusions are drawn: (1) Facb possesses the same antigen-combining capacity as the whole antibody; (2) C1 fixation is normal; (3) The capacity to sensitize target cells to lysis by cytotoxic K cells is lost; (4) Facb—antigen complexes are unable competitively to inhibit phagocytosis of sensitized bacteria by neutrophils.

Effector activating determinants on IgG. I. The distribution and factors influencing the display of complement, neutrophil and cytotoxic B-cell determinants on human IgG sub-classes.

It was possible to demonstrate complement fixation by IgG1 and IgG3 sub-class myeloma proteins which had been heat aggregated under standard conditions. Phagocytosis of bacteria by neutrophils was inhibited by IgG1, IgG2 and IgG3. Lysis of antibody-sensitized target cells by cytotoxic B lymphocytes was inhibited by all four sub-classes of IgG.

Cytotoxicity against human leukaemic cells. I. Demonstration of antibody-dependent lymphocyte killing of human allogeneic myeloblasts.

Antibodies which are to induce the killing of allogeneic myeloblasts by normal lymphoid cells have been found in a high proportion of patients with acute myeloid leukaemia. The cytotoxic mechanism induced by this antibody activity is shown to be highly effective in terms of the number of myeloblasts which can be killed by a given number of lymphoid cells and the antibody concentration needed to induce killing. Reasons for the failure of this cytotoxic mechanism, assuming that antibodies occur against autologous myeloblasts, are suggested by studies in which the cytotoxic lymphoid population has been monitored serially.

Circulating immune complexes in inflammatory bowel disease.

Evidence for circulating immune complexes in sera of patients with ulcerative colitis or Crohn's disease is described. Such sera produced significantly greater inhibition of antibody-induced cytotoxicity mediated by lymphocytes than did sera from normal control subjects. Inhibitory activity of patients' sera showed a positive correlation with severity of disease, the height of the ESR and, in the case of ulcerative colitis, with the severity of inflammation as seen at sigmoidoscopy.

Immunosuppressive consequences of radiotherapy and chemotherapy in patients with acute lymphoblastic leukaemia.

Assays of lymphocyte subpopulations and function have been performed on patients with acute lymphoblastic leukaemia still in remission after 18 months' treatment. The patients were subjects of a trial of the value of craniospinal irradiation in the third month of treatment in preventing central nervous system relapse. Effects of both irradiation and chemotherapy were observed.

Lymphocyte sensitivity to skeletal muscle in patients with polymyositis and other disorders.

The transformation response of peripheral blood lymphocytes to human muscle antigen has been studied in patients with polymyositis, polymyalgia rheumatica and rheumatoid arthritis. Lymphocytes from patients with polymyositis and polymyalgia rheumatica, but not rheumatoid arthritis, showed transformation responses significantly higher than those in control groups, and the highest responses were found in patients with evidence of the most active clinical disease at the time of testing. The significance of finding hypersensitivity to crude muscle antigen in both these conditions is discussed.

Macrophage dependent protection of tumour cells.

Rat lymphoma cells sensitized with antibody and incubated with normal macrophages were shown to become resistant to damage from cytotoxic antibody and complement or cytotoxic lymphocytes. Both lymphoma specific antibody and normal macrophages were required to produce protection. The cytotoxic effect of lymphocytes or antibody with complement and the protective effect of antibody with macrophages was assessed by Cr release and by loss of capacity of lymphoma cells to transfer the disease to syngeneic rats.

Selective deficiency of cytotoxic B lymphocytes in man.

A patient is described with macroglobulinaemia, a variety of autoantibodies, and gross deficiency of lymphocytes showing cytotoxicity against antibody-sensitized target cells . Antibody production in response to tetanus toxoid, delayed hypersensitivity to tuberculin, and lymphocyte transformation with phytohaemagglutinin are normal. The patient's macrophages have normal phagocytic activity against sensitized sheep red cells.

The distribution of antibody and antibody-producing cells after immunization with xenogeneic cells.

After intradermal injection of xenogeneic cells, antibody producing cells were demonstrated in the regional lymph nodes and peritoneal fluid as early as 5 days post-immunization. By 19 days antibody-producing cells were also found in the bone marrow, spleen and peripheral blood. They were not found in significant numbers in the thymus or non-regional lymph nodes.

Evidence for correlation between the antigenic specificity and charge of human IgG. A study of antibody-inducing lymphocyte mediated cell damage.

This study has investigated the charge of IgG involved in antibody dependent lysis of cells by lymphocytes. The following conclusions are drawn: 1. That under certain conditions the physical alteration of IgG can result in molecules which compete with antibody bound to target cell antigens for receptors on cytotoxic lymphocytes.