HLA-G inhibits the allogeneic proliferative response.

HLA-G is a non-classical MHC class I molecule expressed at the feto/maternal interface where it plays a role in materno-fetal tolerance by inhibiting NK cells. Expression of killing inhibitory receptors capable of interacting with HLA-G on T lymphocytes led us to hypothesize that HLA-G molecules could also modulate T cell responses, analyzed here in the context of the allogeneic proliferative response. Using LCL-HLA-G transfectants as stimulators of T cells present among peripheral mononuclear cells and K562-HLA-G1 transfectants as inhibitors in a classical mixed lymphocyte reaction, we showed that HLA-G is able to inhibit T cell allo-proliferation. These findings provide new insight into the role of HLA-G in preventing allograft rejection.     

Recombinant interferon alpha can induce rearrangement of T-cell antigen receptor alpha-chain genes and maturation to cytotoxicity in T-lymphocyte clones in vitro.

T-cell receptor genes are found in the germ-line configuration as well as in rearranged forms, as detected in T lymphocytes by different patterns in Southern blot analysis. We have recently shown that cytotoxic T-lymphocyte (CTL) "precursor" clones, in which rearrangements are not detected in the gene encoding the T-cell receptor alpha-chain (TCRA), acquire specific lytic function induced by treatment with recombinant interferon alpha or gamma. We now report that, coincident with the acquisition of cytotoxic function by the precursor CTL clone; recombinant interferon alpha appears to induce a rearrangement of TCRA. In addition, in a mature CTL clone (i.e., one already showing lytic function) in which one TCRA allele is rearranged, treatment with recombinant interferon alpha appears to induce a new rearrangement of a TCRA gene.     

Excess of maternal HLA-DR3 antigens in HLA DR3,4 positive Type 1 (insulin-dependent) diabetic patients

Summary The susceptibility determinants of Type 1 (insulin-dependent) diabetes mellitus are known to be associated with both HLA-DR3 and DR4. In our study we wished to determine if the parental origin of these antigens could influence susceptibility to the disease. We analysed the inheritance of DR3 and DR4 haplotypes from the father or mother (DR3p, DR4p, DR3m and DR4m, respectively), in the index cases and in the affected and non-affected siblings of 246 diabetic simplex and 41 multiplex families without affected parents. An independent series of 80 multiplex families (GAW 5) was also studied. Among the DR3,4 positive index cases and affected siblings, the paternal and maternal DR3 and DR4 antigens were not distributed randomly: 62% and 72%, respectively, had received DR4 from their father and DR3 from their mother (DR4p/DR3m), while only 38% and 28%, respectively, had received a paternal DR3 together with a maternal DR4 (DR3p/DR4m). This differed significantly from the 50% expected ratio (p<0.01) and was not observed in unaffected siblings. No excess of maternal DR3 in the absence of DR4 and no excess of paternal DR4 in the absence of DR3 were observed. The finding suggests that some maternal DR3 related event (presumably during pregnancy) might play an enhancing role in the pathogenesis of Type 1 diabetes. It also implies that siblings with both DR4p and DR3m have a significantly higher risk for disease than those with DR3p and DR4m.     

HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS : II. INFLUENCE OF THE DL-A SYSTEM OF CANINE HISTOCOMPATIBILITY UPON THE SURVIVAL OF CARDIAC ALLOGRAFTS

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration.