EdmondJ Yunis

DEPRESSED MATERNAL LYMPHOCYTE RESPONSE TO PHYTOHÆMAGGLUTININ IN HUMAN PREGNANCY

Abstract There is a significant reduction in the maternal lymphocyte response to phytohaemagglutinin (P.H.A.) in most pregnant women. Plasma in 10% concentration from pregnant women does not reduce the lymphocyte responses of non-pregnant controls to P.H.A. These findings support the hypothesis that there is depressed cell-mediated immunity in pregnant women as shown by the reduction in lymphocyte responses to P.H.A., certain microorganisms, malignancies, homografts, and the conceptus.

SUCCESSFUL FETAL LIVER TRANSPLANTATION IN A CHILD WITH SEVERE COMBINED IMMUNODEFICIENCY

Following transplantation with allogeneic fetal liver, a boy with a severe combined immunodeficiency and adenosine-deaminase (A.D.A.) deficiency developed immunocompetent T and B cells in an orderly manner. Engraftment was indicated by appearance of A.D.A. activity and donor-lymphocyte and red-cell antigens. The child remained free of major infections until one year later when he developed an ultimately fatal nephrotic syndrome associated with immune-complex glomerulonephritis.

EFFECT OF BLOOD-BANK STORAGE ON LEUCOCYTE FUNCTION

Abstract The bactericidal activity of polymor-phonuclear neutrophils (P.M.N.s) and the ability of lymphocytes to respond to phytohaemagglutinin (P.H.A.) were studied in blood drawn under standard blood-bank conditions into acid-citrate-dextrose anticoagulant and stored at 4°C. There was no loss of bacteridical activity during the first 24 hours of storage, and bactericidal activity was not completely lost until after 4 days of storage. Lymphocytes lost the ability to respond to P.H.A. after 17 days of storage although morphologically normal lymphocytes were present in blood stored for 21 days. Irradiation with up to 6000 roentgens reduced but did not eliminate the lymphocyte response to P.H.A. and did not affect the bactericidal capacity of the P.M.N.S. These results suggest that functionally active P.M.N.S are present in bank-blood during the first few days of storage or may be separated and stored for periods considerably longer than previously indicated. The presence of morphologically normal lymphocytes and responsiveness to P.H.A. stimulation indicate that any bank-blood within the 21-day shelf-life may be the source of a potential graft-versus-host reaction when transfused to patients with impaired immune responses. Irradiation of the blood apparently does not protect against this hazard.

TREATMENT OF SEVERE COMBINED IMMUNODEFICIENCY WITH BONE-MARROW FROM AN UNRELATED, MIXED-LEUCOCYTE-CULTURE-NONREACTIVE DONOR

A 7-month-old boy with severe combined immunodeficiency had no relative who was a suitable bone-marrow donor as determined by mixed-leucocyte-culture (M.L.C.) testing. In the general population an M.L.C.-nonreactive, unrelated donor was found among individuals who were identical with our patient at the Four locus. Following a bone-marrow transplant this child showed signs of rapid immunological reconstitution and only a mild graft-versus-host reaction. Unfortunately, the child died 31 days post-transplantation of cytomegalovirus infection. The findings support the hypothesis that matching for lymphocyte-defined antigens among unrelated individuals will permit successful immunological reconstitution.

ON THE NATURE OF IMMUNOLOGICAL TOLERANCE

Abstract The nature of immunological tolerance has been enigmatic. Using a cobra-venom inhibitor which reduces haemolytic complement activity of mouse serum both in vitro and in vivo, it has been possible to inhibit development of immunological tolerance to human γ-globulin (H.G.G.). B10.D2/Sn old line mice which are characterised phenotypically by failure to produce the fifth component of complement are also defective in development of tolerance to this same antigen. It is postulated that induction of tolerance includes specific destruction of a line of cells by interaction of antibody first produced and located on the surface of the cells with haemolytic complement.

B-CELL ALLOANTIGEN ASSOCIATED WITH CHRONIC MESANGIOCAPILLARY GLOMERULONEPHRITIS

Thirteen patients with chronic mesangiocapillary glomerulonephritis (M.C.G.) defined by light and immunofluorescent microscopy were examined for possible B-lymphocyte alloantigen associations by means of antisera from multiparous mothers of M.C.G. probands. Three such sera reacted with M.C.G.-patient B-cells. One of these sera (M.C.G.3) was highly discriminative for a B-cell antigen present in 77% of M.C.G. patients and only 17% of normal individuals tested. The risk of developing M.C.G. was estimated to be 16-6 times greater in the presence of the M.C.G.3 antigen than in its absence. This is the first demonstration of an association between a specific B-lymphocyte determinant and immune-mediated glomerulonephritis.

FUNCTIONAL ACTIVITY OF A CHEMICALLY INDUCED THYMIC SARCOMA

Abstract Thymic tumours were induced by direct intrathymic injection of 7,12-dimethylbenzanthracene in newborn mice. Most of these tumours were malignant lymphomas and two were thymic reticulosarcomas. One of the thymic reticulosarcomas proved effective in the restoration of body growth, survival-rates, lymphoid development, and homograft immunity in neonatally thymectomised syngeneic mice grafted subcutaneously with the thymic tumour. It seems most likely that this tumour functions by means of a humoral or inductive factor operating at long range.