Concentrations of linoleic acid in adipose tissue differ with age in women but not men.

Samples of adipose tissue, taken post-mortem from the anterior abdominal wall near the umbilicus, were obtained from road-accident victims in the Aberdeen area; subjects were of either sex with a wide age distribution (7-88 years). Similar samples were obtained from elderly females (mean age 77) who had died in Aberdeen Royal Infirmary from a variety of causes. Fatty acid compositions of samples were determined by capillary gas chromatography of methyl esters, which were obtained by direct esterification of the adipose tissue. The mean linoleic acid content for all samples was low compared with published values for similar samples from Europe and North America. Cumulative frequency distribution curves for linoleic acid did not differ with age in males but significant differences (P less than 0.001) occurred in females, with decreased concentrations in those aged over 60 compared to younger groups. Concentrations of trans-unsaturated fatty acids ranged between 2 and 7 per cent but did not differ significantly between groups. Low adipose concentrations of linoleic acid are regarded as a reflection of its reduced long-term dietary intake and as a risk factor for the development of coronary heart disease.

The role of class I and class II MHC antigens in the rejection of vascularized heart allografts in mice.

We have examined the role of entire major histocompatibility complex (MHC) disparity, individual class II or class I alloantigens in the rejection of vascularized heart allografts. Our results demonstrate that entire MHC, as well as both class II and class I disparities, may induce acute heart graft rejection or severe and irreversible heart muscle destruction. However, in 1 of 2 combinations differing at class II and 1 of 5 differing at class I, hearts have shown a good function greater than 100 days postgrafting. Furthermore, each donor-recipient combination has demonstrated a unique pattern of heart allograft function as well as a degree of heart muscle damage. In conclusion, these data suggest that the rejection process depends upon multiple factors such as the immune-response-gene-regulated immunoresponsiveness of the recipient as well as the expression of alloantigens on heart grafts during the induction and effector phases of the immune response.

Induction of transplantation tolerance in rats by spleen allografts. III. The role of T suppressor cells in the induction of specific unresponsiveness.

Heterotopic (WAG x AGUS)F1 spleen allografts survive indefinitely when transplanted to normal AGUS recipients and induce long-term donor-specific unresponsiveness. In this report, we have examined the immune reactivity of spleen graft recipients soon after transplantation, in an attempt to define the immunological mechanisms responsible for the induction of donor-specific unresponsiveness. Unresponsiveness develops as early as one week after splenic transplantation. T cells obtained from the recipient lymph node and spleen exhibit reduced mixed lymphocyte reaction responses to donor (WAG) but respond normally to third-party (PVG) stimulators. In contrast, T cells obtained from the spleen graft are unresponsive to both donor and third-party stimulators. Donor specific T suppressor cells (Ts) appear in the recipient's lymph node and spleen by one week posttransplantation--however, at this time antigen nonspecific suppressor cells predominate in the spleen graft. Only minimal cytotoxic T cell activity could be detected in the spleen graft, with the host spleen and lymph nodes being devoid of cytotoxic T lymphocytes. Sera obtained one or two weeks following splenic transplantation did not contain cytotoxic alloantibodies, and only a very weak response could be detected at one month. These data demonstrate that the unresponsiveness associated with the spontaneous acceptance of spleen allografts is correlated with the early induction of antigen specific Ts in recipient lymphoid tissue and the presence of nonspecific suppressor cells at the graft site.

Induction of transplantation tolerance in rats by spleen allografts. II. Evidence that W3/25+ T suppressor/inducer and OX8+ T suppressor/effector cells are required to mediate specific unresponsiveness.

The results presented in this report demonstrate that T cells, isolated from AGUS rats bearing long-term (WAG X AGUS)F1 spleen allografts adoptively transferred to irradiated AGUS recipients could not mediate the rejection of WAG hearts but rejected PVG. A hearts in acute fashion. Further, unresponsive T cells were able to suppress the capacity of adoptively transferred (40 X 10(6) normal T cells to reject WAG but not PVG.A heart allografts. We also studied the role of W3/25+ and OX8+ T cells subsets in the maintenance of unresponsiveness. Isolated W3/25+ or OX8+ unresponsive T cells were not able to mediate acute rejection, but were less effective in prolonging WAG allograft survival than the unresponsive whole T cell population, suggesting that both W3/25+ Ts1 and OX8+ Ts2 subsets were required for effective suppression in vivo. When, however, unresponsive W3/25+ T cells were infused simultaneously with normal OX8+ T cells, they could produce indefinite survival of WAG heart allografts. These results indicate that the unresponsive state induced by (WAG X AGUS)F1 spleen allografts transplanted to AGUS rats is maintained by the interaction of W3/25+ T suppressor/inducer and OX8+ T suppressor/effector cells.

The role of TDTH and Tc populations in organ graft rejection. I. Functional analysis of graft-infiltrating T cells.

To analyze the role of T cell subpopulations in the rejection of organ allografts, we developed a new model for obtaining large numbers of graft infiltrating cells (GICs). We isolated W3/25+ Th/DTH and OX8+ Ts/c from vascularized, irradiated rat spleen allografts. W3/25+ GICs obtained from spleen allografts transplanted to normal recipients were highly effective in eliciting cardiac allograft rejection when transferred to sublethally irradiated recipients, however, the OX8+ subset was incapable of eliciting rejection. On the other hand, when OX8+ GICs were obtained from spleen allografts transplanted to previously immunized recipients, they were as efficient as the W3/25+ Th/DTH subset in eliciting cardiac allograft destruction. These results indicate that the W3/25+, OX8- T cell is required for the rejection of primary organ allografts, but that the rejection of a secondary allograft by an immune recipient may be mediated, independently, by both W3/25+ and OX8+ cells.

Structure of a class I gene from Syrian hamster.

Syrian hamsters possess a multigene class I family yet fail to perform several associative immunologic functions. In an attempt to determine whether representative hamster genes are structurally functional, we have cloned two closely linked class I-like genes and determined the complete sequence of the 5' member. Its exon organization is similar to that seen in mouse and man, although only two intracytoplasmic domains are encoded instead of the usual three. Comparison of the predicted amino acid sequence and the 3' untranslated region to mouse and human genes suggest along with the linkage data that the hamster gene may be related to either or both K and Qa region genes but probably not to D and L region genes.

Induction of transplantation tolerance in rats by spleen allografts. I. Evidence that rats tolerant of spleen allografts contain two phenotypically distinct T suppressor cells.

We have examined suppressor cell activity in transplantation tolerant (TT) rats bearing vascularized spleen allografts in several different donor-recipient combinations. More than 60% of WAG (RT-1u) and 65% of AGUS (RT-1l) spleen allografts were permanently accepted when transplanted to AGUS and PVG (RT-1c) rats, respectively. All (WAG X AGUS)F1 to AGUS and (AGUS X PVG)F1 to PVG spleen allografts survived indefinitely. Unseparated LNC, TDL, and whole T cell or W3/25+, OX8- T cell populations obtained from AGUS rats bearing (WAG X AGUS)F1 spleens exhibited reduced mixed lymphocyte reaction (MLR) responses to the spleen donor, and to some extent to BN(RT1n) third-party stimulators, but responded normally to PVG.A(RT1a) stimulators. Coculture experiments demonstrated that lymph node cells (LNC) and thoracic duct lymphocytes (TDL) of TT rats contain RT1 specific suppressor cells. Furthermore, T cells isolated from all donor-recipient combinations contained two phenotypically distinct suppressor cell populations: a radiosensitive W3/25+, OX8- (Th/i) and a relatively radioresistant W3/25-, OX8+ (Ts/c). These Ts may be responsible for the maintenance of TT.

Phylogenetic conservation of immunoglobulin heavy chains: direct comparison of hamster and mouse Cmu genes.

We have analyzed the JH-Cmu locus of the Syrian hamster by DNA cloning and sequencing. The single Cmu gene is highly homologous to that of the mouse. The hamster equivalents of the JH and switch (S) recombination regions are arranged as in the mouse, but surprisingly are not highly conserved. Also unlike its close murine relative, the Smu regions among inbred hamster strains are not polymorphic. The complete nucleotide sequence of hamster and mouse Cmu genes have been compared to partial Cmu sequences of other species. Conservation within a portion of the 3' untranslated region may signify functional requirements for 3' end processing. Mutational frequencies within exons and introns of hamster and mouse do not support the theory that the rate of DNA transitions to transversions decreases with evolutionary distance.

Syrian hamster DNA shows limited polymorphism at class I-like loci.

The class I gene products of the Syrian hamster major histocompatibility complex are unique in that they lack functionally detectable polymorphism. Mouse cDNA and hamster genomic probes were used to analyze the hamster class I gene family using genomic Southern hybridization. These studies revealed that the hamster possesses a complex class I multigene family and that it shares extensive sequence homology with the corresponding mouse sequences. Unlike the mouse, however, the Syrian hamster demonstrates only limited restriction endonuclease polymorphism in these genes. These results suggest that the lack of detectable polymorphism in this species is directly related to limited DNA polymorphism. The data presented here support the hypothesis that this species has undergone an evolutionary bottleneck, i.e., that all surviving members of the species arose from a limited number of progenitors.

Antigen-specific xenogeneic CTL activity in the Syrian hamster.

Previous studies of the Syrian hamster have demonstrated a lack of cytotoxic T lymphocyte (CTL) activity in vaccinia virus-infected animals. Our laboratory has reexamined CTL activity in both the classical inbred strains, MHA, CB, and LSH, as well as the recently inbred strain MIT. Primary and secondary CTL specific for the immunizing antigen have been detected after in vitro culture in MIT but were not demonstrable in the classical strains. Only lymph node cells of the responding animal demonstrated this activity, spleen cells being phenotypically devoid of such a response. Identification of the cell responsible for cytolysis as a T cell was demonstrated by nylon wool nonadherence, specificity on Con A blasts, and the lack of surface immunoglobulin, as demonstrated by cell-sorter analysis.

Suppressor cells in the thoracic duct lymph of tolerant, spleen-grafted rats.

Vascularized spleen allografts between two different inbred rat strains induce specific transplantation tolerance in vivo. Thoracic duct lymphocytes isolated from tolerant rats exhibited notable nonresponsiveness to donor stimulator cells in the mixed lymphocyte reaction. In-vitro co-culture experiments indicate that this nonresponsiveness reflects the activity of both specific and nonspecific suppressor cells. Since suppressor cells are present in tolerant animals, it is possible that the suppressor cells play an important role in maintaining spleen-induced transplantation tolerance.

Foot reflexes and the use of the "inhibitive cast".

The four diametrically opposed tonic reflex movements of the foot that can be elicited in normal children throughout the first year represent the peripheral segments of proximally cascaded reflex balance recovery systems. Clinical persistence of one or more of these obligatory movements in cerebral palsied children may habitually distort foot posture and recruit proximal reflex muscle activity and associated hypertonus. Inhibitive casting has proved to be a significant useful adjunct for management of both foot deformity and associated proximal hypertonicity.