The families of 29 patients with systemic lupus erythematosus and 42 normal subjects were studied to determine the inheritance of the HLA-A, B, C, and DR antigens and also the complement polymorphisms for C2, C4A, C4B, and Bf, which are encoded in the same region of the sixth chromosome. Null (silent) alleles for C4A, C4B, or C2 were found in 24 of the 29 (83%) patients compared with 18 of the 42 (43%) normal controls. HLA-DR3 was present in 20 (69%) of the patients and seven out of 39 (18%) of the normal controls. There was strong linkage disequilibrium between DR3 and the null alleles for C4A and C4B.The data did not permit the relative contributions of DR3 and null factors of C4A and C4B as genetic risk factors to be distinguished. The Al, B5, B7, B8, DR2, and DR3. The importance of these associations remains uncertain, but one possibility is that they reflect linkage disequilibrium with other loci that determine risk factors. In this context the HLA region encoded complement polymorphisms C2, C4A, C4B, and Bf may be relevant candidates. The polymorphism is particularly complex and extensive for the C4A and B loci.5 In addition to the expressed polymorphic variations null (silent) alleles for C2 and both C4 loci have been described," 8 and these are associated with no detectable product. Furthermore, variation in haemolytic activity between the C4 gene products has been observed, and one, C4A6, is nonhaemolytic when inherited in certain haplotypes. 9 Proved complement deficiency states account for only a small minority of cases of systemic lupus erythematosus, but no
Results appear to justify the continued use of volunteer donors in chronic-phase chronic myeloid leukemia, but infection and chronic GVHD are still major problems.
Proliferative T cell responses against major histocompatibility complex (MHC) incompatible stimulator cells in the mixed lymphocyte reaction are conventionally regarded as primary. However, it is generally accepted that the recognition of allogeneic MHC products results from a cross-reaction by self-MHC-restricted cells. These two assumptions were tested by examining the contribution of previously primed and naive T cells to 'primary' alloresponses. Peripheral blood T cells were separated into LFA-3+, memory, and LFA-3-, naive, populations by fluorescence-activated cell sorting. In contrast, to recall antigen responses to Candida albicans which were almost entirely confined to the LFA-3+, memory, population, the proliferative response to MHC incompatible stimulator cells, including HLA-DR-expressing mouse L cell transfectants, was equally distributed between the two T cell subsets in 5 day assays. Furthermore, limiting dilution analysis showed that the frequency of alloreactive T cells did not differ significantly between the two populations. The kinetics of proliferation in the two populations differed but were consistent with their naive and memory phenotype, in that after 3 days of culture the LFA-3+ cells proliferated more strongly to MHC alloantigens. These results show that a substantial proportion of 'primary' alloresponses are contributed by previously primed cells. In addition, the evidence for the cross-reactive hypothesis is supported and extended from the clonal to the population level.
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