Major histocompatibility complex control of NK-related allogeneic lymphocyte cytotoxicity in rats. The contributions of strong and medial transplantation antigens.

Allogeneic lymphocyte cytotoxicity (ALC) describes the elimination of allogeneic lymphocytes in vivo by an NK-related activity. There is evidence that ALC is demonstrable between donor and recipient when these are incompatible at MHC gene loci alone. Since ALC is a property of T cell-deficient nude rats, the role of the MHC in this rejection process needs further study. We have determined the contribution of the MHC to ALC using congenic and recombinant rats. In our analysis we have assumed that ALC involves the recognition of classic alloantigens by clonally distributed effector cells as for other examples of transplant rejection, although this is not yet proved. Strong ALC was measured between congenic rats that differed for MHC genes only. Non-MHC incompatibility alone did not elicit ALC. In the presence of MHC incompatibility the strength of ALC generated in a recipient was dependent on non-MHC genes. The PVG background generated high ALC responses whereas ALC was not measured in the DA rat. However ALC was measured in the congenic PVG-RT1avl (DA) rat. The contributions of classic class I (RT1.A), class II (RT1.B/D), and medial transplantation (RT1.C) regions of the rat MHC were determined by comparing different recombinant donors into the same recipient strain. Single region differences alone in any of these three MHC regions did not elicit full ALC. In two sets of transfers a combination of RT1.B/D and RT1.C region incompatibility was sufficient to generate a full allogeneic response. It can be concluded that the controlling element for allogeneic lymphocyte cytotoxicity is in the RT1.B/D-RT1.C region of the rat MHC.

The effects of Depo-Provera on serum protein levels in Nigerian women.

The concentration of 13 serum proteins were determined in 50 women who had received the 3-monthly intramuscular injection of Depo-Provera for contraception over a mean period of 18 months and 40 women of comparable ages who served as controls. Sera from fasting subjects were used to determine the levels of each specific protein by quantitative immunodiffusion technique. Treatment with Depo-Provera produced increased serum levels of albumin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, haptoglobin IgG; reduced levels of alpha 1-antitrypsin, transferrin, C3c, C4 but no change in serum IgA, IgM, C-reactive protein and ceruloplasmin. The significant alterations were observed in serum proteins that are notably synthesized by the liver, an observation consistent with the influences which gonadal hormones exert on the metabolic activities of this organ.

Alterations in blood lipids and side effects induced by depo-provera in Nigerian women.

A fasting plasma lipid profile investigation was undertaken in 63 women who were on contraception with the 3-monthly intramuscular depo-provera injection for periods ranging from 3 to 30 months. Fifty nulliparous women, with no previous history of contraceptive therapy, matched for age, parity, height and socio-economic status, served as controls. History of clinico-physiological side effects was recorded. The results show reduced levels of fasting plasma cholesterol in patients on depo-provera compared to the control group but there was no significant change in fasting plasma phospholipid levels. Contrary to expectations, the patients on depo-provera had higher fasting plasma triglyceride levels than controls. Excessive weight gain and irregular heavy bleeding represent major reasons for withdrawal from depo-provera therapy. The findings suggest that the alterations in the plasma lipid profile, body weight and side effects experienced by women on depo-provera may be inversely related to the duration of effective therapy.

Enzyme-induced modification of the surface properties of lymphoid cells in malignant disease. I. Effect of trypsin on rosette formation by lymphocytes in myelomatosis.

The surface properties of blood lymphocytes from treated myeloma patients and healthy controls were studied in vitro. The patients were tested 6 weeks after the last treatment to allow time for cells to recovery from possible drug toxicity. Peripheral-blood lymphocytes were tested for rosette formation with unsensitized sheep erythrocytes (E rosettes) and with complement and antibody-coated erythrocytes (EAC rosettes). The tests were duplicated using lymphocytes pretreated with trypsin. As others have noted, myelomatosis is associated with increased blood levels of EAC-rosette-forming cells and a marked reduction in E-rosette-forming cells. E-rosette formation was significantly increased by pretreatment of myeloma lymphocytes with trypsin. By contrast, enzyme-treated cells showed no significant change in EAC-rosette formation. These results suggest that the absolute number of circulating T cells is probably not reduced in myelomatosis, but that the surface of T cells is somehow modified so that a proportion of them lose the ability to form E rosettes.