The Effect of Skin Homograft Rejection on Recipient and Donor Mixed Leukocyte Cultures

Abstract

The discovery of the mitogenic (1) and lymphocyte transforming (2) properties of phytohemagglutinin (PHA) was soon followed by the finding that many antigens (3, 4) and vaccines (5) were also able to stimulate peripheral lymphocytes to proliferate in short-term cultures, provided the cell donor had been previously sensitized with the antigen. Histocompatibility antigens also produce lymphocyte transformation and mitoses without preceding sensitization in mixed leukocyte cultures of unrelated individuals (6). As the genetic relationship increases from unrelated subjects to siblings, and thence to identical twins, the lymphocyte proliferation of their mixed leukocyte cultures diminishes (7). The degree of lymphocyte transformation in mixed leukocyte cultures has also been reported to be proportional to the degree of cross-reactivity of graft rejection of the subjects' skin by a third unrelated recipient (8). To define further the relationship between lymphocyte transformation and homograft rejection we have investigated the changes in the reaction of mixed leukocyte cultures of graft recipients and a donor temporally before, during, and after first and second skin transplants (9). MethodsThe 3 subjects were two female graft recipients, "A" and "B" aged 44 and 49 years respectively, and a 61-year-old male graft donor, "C." Patient A had an exacerbation of her recurrent keratoacanthoma, but was free of any systemic symptoms except for a transient episode of iron deficiency anemia during the latter part of the study after the second skin grafting. Both patients B and C had a history of malignant melanoma, but were asymptomatic and had been free of any recurrent disease for more than 5 years. The subjects had not received immune suppressant therapy for more than a year prior to the study. All 3 had normal gamma globulin levels as determined by serum protein electrophoresis and normal febrile agglutination titers to the Salmondlae groups. Subjects B and C were tuberculin (PPD intermediate strength) 1 positive, but A was not.

DNA Synthesis in vitro in Leukocytes from Patients with Ataxia telangiectasia

“…O ppenheim et al (10) observed an enhanced response to PHA in vitro of lymphocytes from patients with ataxia telangiectasia during homograft rejection. Similar results were obtained with lympho cytes from normal individuals during homograft rejection (34,35).…”

The Mixed Leucocyte Reaction: Studies Using Leucocytes From Unrelated Human Subjects

“…The findings that the MLR was negative in cultures of lymphocytes from monozygotic twins [2,11] and that the incidence of negative reactions in cultures of leucocytes from siblings was greater than in cultures from un related subjects [1,3,4,5] suggests that the reaction has a genetic basis. The increased 'strength' of reaction in cultures made after skin grafting the subjects [3,14] supports the view that histo compatibility antigens may determine the degree of lymphocyte transformation, and it was suggested that only the strongest histo compatibility locus was important in determining the degree of reaction [11]. Studies of the MLR in inbred rat strains have indicated…”

Leukocyte Antigens and the Mixed Lymphocyte Culture Reaction

“…It was proposed to explore the mixed lymphocyte culture reaction (MLR) as a potential histo compatibility test in vitro [3,1]. This view was supported by the finding that the number of transformed cells in MLR of skin graft donors and recipients increased at the time of graft rejection [11].…”