Regulation of nursing in chimpanzees.

The regulation of nursing was studied in captive chimpanzees from birth to 6 months of age. It was asked whether regulation was predictable or timing was irregular. A search for unimodal frequency distributions resulted in a distinction among nursing bouts, nursing episodes (bouts with brief interruptions) and nursing pauses. The frequency distributions of these types were either normal with very large standard deviations or exponential (i.e., randomly terminated). This implies a very irregular timing. Longer nursing episodes were followed by somewhat longer pauses; pauses with daytime sleep (that were relatively long) were followed by longer nursing. However, these regulatory effects were only slight. Most of this loose regulation of nursing was due to the infant, as the mothers did not put the infant on the breast and usually were permissive. Comparisons with humans suggest a similarly loose organization as well as frequent feeding in societies that provide relatively unlimited access to the breast. The regular 4-hr, meal-like schedule in industrial countries seems mainly to be due to human mothers and their advisors.

Polymorphism for RhT3, a CD3-like cell surface antigen, expressed on rhesus monkey T lymphocytes.

The target antigen of the FN18 monoclonal antibody, called RhT3, is probably the rhesus monkey homologue of the human CD3 antigen, expressed on mature T cells. RhT3 appears to be polymorphic, since FN18 was not reactive with T cells from all the screened animals. Thus, immunofluorescent staining of peripheral blood lymphocytes with FN18 antibody revealed either a positive or a negative phenotype for the target antigen. In a rhesus monkey population, nonreactivity for FN18 was observed in low frequency (2.7%). Expression and non-expression of RhT3 appeared to be constant characteristics. Non-expression was not associated with any demonstrable immunodeficiency. Further, there seemed to be no association between the presence of the FN18 target antigen and sex, age or expression of MHC class I antigens. Family studies indicated that the positive phenotype is expressed in the same fashion by animals presumably heterozygous or homozygous for the positive allele, the negative phenotype being expressed only on cells from animals homozygous for an assumed blank allele. Therefore, the positive phenotype is likely to be transmitted in an autosomal dominant mode. In the animals with the negative phenotype, normal T-cell numbers were present, as was demonstrated by B- and T-cell specific monoclonal antibodies. Cytoplasmic staining of cytospun lymphocyte preparations with FN18 revealed that polymorphism was present at the intracellular level. Cell proliferation tests, using PWM and Con A as mitogens, showed the presence of apparently functional RhT3 cell surface molecules in FN18 non-reactive animals. Polymorphism is therefore assumed to be at the epitope level.

Platelet and granulocyte specific allo-antigens in chimpanzees.

Chimpanzees were allo-immunized with blood from donors, ChLA-A and -B identical to the recipient. The sera of some of these animals contained antibodies that reacted only with the platelets or granulocytes of the immunizing donor and of some related and unrelated chimpanzees. Both for the platelets and the granulocytes a di-allelic system of allo-antigens is described, provisionally called ChPL-1 and ChGR-1.

The major histocompatibility complex of rhesus monkeys, RhLA: XV. Chemical characterizations of DR locus antigens and antigen 48.

Immunoprecipitation studies of the rhesus monkey major histocompatibility system have shown that the RhLA-DR locus codes for class II antigens with molecular features that are homologous to the class II antigens coded for by the human HLA-DR locus. The product of another alloantigenic RhLA-linked locus of the rhesus monkey, called '48', is provisionally characterized as a class I system.

Kidney transplantation in rhesus monkeys. Matching for D/DR antigens, pretransplant blood transfusions, and immunological monitoring before transplantation.

The effect of matching for D/DR antigens and of three pretransplant blood transfusions on kidney allograft survival was investigated in unrelated rhesus monkeys treated with standard immunosuppression. A control group consisting of host-donor combinations mismatched for one or two DR antigens (mixed lymphocyte culture (MLC) positive) and not receiving transfusions showed a MST of 13 +/- 1.2 days with a range from 9 to 22 days. The administration of pretransplant blood transfusions led to a MST of 28 +/- 5.4 days with 5 of 12 animals showing survival times of more than 22 days (i.e., a bimodal distribution of survival times). Recipients matched with their donors for two DR antigens and given transfusions showed an even better MST of 39 +/- 4.0 days. Under these conditions, MLC-negative combinations fared slightly better than MLC-positive ones: only 1 of 10 animals showed a survival time of less than 22 days and kidney function in the first weeks after transplantation was significantly better. When mixed lymphocyte reactions (MLC reactivity) between host and donor before and after the transfusions were compared, it was possible to predict to some extent the eventual fate of an allograft: increased mixed lymphocyte reaction predicted relatively short survival times, decreased mixed lymphocyte reaction relatively long ones (P less than 0.01).

The major histocompatibility complex of rhesus monkeys. XIV. A family study of DR and other RhLA-linked cell membrane antigens.

The segregation of B-cell specific (Ia) determinants was studied in a large number of rhesus families. As expected, on the basis of results of a recent population study, the eight serologically defined DR antigens segregated as alleles of a single locus within RhLA. Two or three antigens not controlled by DR remained candidates for a second Ia series closely linked to DR. The 162 identifiable haplotypes provided interesting information regarding positive associations among antigens of two, three or even four sets of RhLA loci. Further, a new series of antigens closely linked to the RhLA-A locus could be postulated. Data obtained from 8 recombinant offspring permitted a better definition of the mapping position of all known loci of RhLA.

Major histocompatibility complex matching and other factors influencing skin allograft survival in related and unrelated rhesus monkeys.

Skin allografting was performed in rhesus monkeys to study the influence of matching for products of the RhLA region and of various other parameters. As expected, the longest mean survival times (MSTs) were observed when donors were RhLA-identical siblings; the MST seemed a bit shorter when grafts from at least two RhLA-nonidentical siblings were simultaneously present. Matching for RhLA-A and B locus antigens was studied in RhLA-haploidentical and in unrelated combinations; in both categories, the MST was about 12 days if there were no A or B antigen disparities, 10 days if there was one A or B disparity, and about 9 days for two or more disparities. A positive effect of matching for D/DR antigens and mixed lymphocyte culture (MLC) nonresponsiveness between host and donor was questionable; additional data are required to confirm the minor beneficial effect observed. With regard to the sex of donors and recipients, female recipients rejected skin allografts more rapidly than did males in related and unrelated combinations. In this respect, females with a known or possible history of pregnancy were not different from nulliparous animals. A possible influence of donor sex on skin allograft survival remained equivocal. The i.v. administration of donor-specific antigen before skin grafting led to a significant prolongation of the MST; in the majority of combinations with prolonged graft survival, B cell-specific antibodies were demonstrable in the recipients' sera. An "enhancing" influence of such antibodies is possible, although the available data do not prove such an effect.

The major histocompatibility complex of rhesus monkeys. XIII. Current knowledge of DR and other B-cell specific antigens.

Results of a population study with all currently available B-cell specific alloantisera indicate that eight antigens controlled by the RhLA-linked DR locus can now be identified. This leaves a gene frequency of about 0.15 for unidentified or "blank" antigens of that locus. Of the nine identifiable Ia antigens which are not controlled by the DR locus, three or four may form the basis of a second series which is probably also controlled by the RhLA region.

The major histocompatibility complex of chimpanzees: identification of several new antigens controlled by the A and B loci of ChLa.

The serology and genetics of 17 serologically defined tissue antigens of chimpanzees is described. Analysis of their distribution in 200 unrelated chimpanzees and their segregation in a large number of chimp families suggests that 14 of the antigens are controlled by two closely linked loci: seven by the A and seven by the B locus of ChLA. Typing of chimpanzees with human alloantisera revealed that several of those A and B locus antigens of ChLA are the chimp's serological counterparts of A and B locus antigens of the human HLA system, respectively. One of the newly discovered chimp antigens may be defined by a "third series" of ChLA, most likely the chimp's analogue of the human HLA-C series. The probable existence of a ChLA-linked D locus of chimpanzees and similarities between D-locus and Ia-locus (DRw) antigens of chimpanzee and man, are also briefly discussed.

The major histocompatibility complex of rhesus monkeys, RhL--A. VII. Identification of five new serologically defined antigens.

Five new serologically defined (SD) tissue antigens of rhesus monkeys are described. Results of a population study and a segregation analysis in families were consistent with their control by the major histocompatibility complex (MHC), as alleles of the two previously established SD loci of RhL--A. The number of identifiable SD specificities of the rhesus monkeys' MHC is now twenty-five, thirteen controlled by the SD1 locus and twelve by SD2. The recombination frequency between SD1 and SD2 is estimated to be 0.3%. No evidence of a third SD series, as analogue of the human HLA--C locus, has yet been found.

The major histocompatibility complex of rhesus monkeys. VI. Serology and genetics of Ia-like antigens.

The serology and genetics of11 new cell surface alloantigens of rhesus monkeys are described: They are controlled by the mamor histocompatibility complex but are distinct from the conventional serologically defined (SD) antigens ofRhL-A. The new specifications are termed "Ia-like" because ofserological, immunocytological and other characteristics reminiscent of Ia-antigens of the mouse. Population and family analyses led to the postulation of two segregant series controlling eight of the 11 Ia-like specificities of the monkey. Strong linkage disequilibria with SD2 antigens and genetic mapping on the basis of segregation studies in recombinant offspring in the monkey families, places at least one of the two loci in the vicinity of the SD2 locus of RhL-A, not in the region of the major MLC or LD1 locus. For this and other reasons, the new B-cell alloantigens of rhesus monkeys are not believed to be similar to or associated with the stimulator antigens of LD1. The biological function(s) of the Ia-like antigens of primates are as yet unknown.

Progress in rhesus histocompatibility typing resulting from the Second International Nonhuman Primate Histocompatibility Workshop (1973).

The Second International Nonhuman Primate Histocompatibility Workshop permitted comparison of rhesus monkey alloantisera developed in various laboratories on a single common panel of related and unrelated monkeys. Analysis of the data permits the conclusion that at least nine specificities are recognized by more than one laboratory, including six at the first locus and three at the second locus.