Cytotoxic T-cell responses to H-Y: mapping of the Ir genes.

The secondary cytotoxic responses to the male specific antigen (H-Y) in in mice show H-2 restrictions so that cytotoxic female cells must share K and/or D end antigen with the male target cells. The production of cytotoxic cells is under the control of Ir genes, thus offering the possibility of studying the function of Ir genes in H-2-restricted cytotoxic responses. There are two kinds of Ir genes regulating this response; the dominant gene in the H-2b haplotype and complementary genes in other haplotypes. Now we have been able to map the dominant gene and some of the complementary genes: the dominant genes is in IAb, and in H-2k/H-2d complementation, the Ir genes are in ICk and ICd, and in H-2k/H2s and H-2k/H-2q complementations, at least the H-2k gene is in IC.

Cytotoxic T-cell responses to H-Y: correlation with the rejection of syngeneic male skin grafts.

The ability of female mice to rapidly reject syngenic male skin grafts is largely determined by dominant genes in the IB region of the H-2b halotype, whereas the ability to produce anti-H-Y cytotoxic cells is determined by a dominant gene in the IA region the H-2b halotype, or by complementary genes in the IC region of some other haplotypes. Thus, it seems that H-2-retricted anti-H-Y cytotoxic T cells are not responsible for the rejection of syngeneic male skin grafts.

The T cell response of HLA-DR transgenic mice to human myelin basic protein and other antigens in the presence and absence of human CD4.

Analysis of HLA class II transgenic mice has progressed in recent years from analysis of single chain HLA class II transgenes with expression of mixed mouse/human heterodimers to double transgenic mice expressing normal human heterodimers. Previous studies have used either HLA transgenic mice in which there is a species-matched interaction with CD4 or mice which lack this interaction. Since both systems are reported to generate HLA-restricted responses, the matter of the requirement for species-matched CD4 remains unclear. We have generated triple transgenic mice expressing three human transgenes, DRA, DRB, and CD4, and compared HLA-restricted responses to peptide between human-CD4+ (Hu-CD4+) and Hu-CD4- littermates. We saw no difference between Hu-CD4+ and Hu-CD4- groups, supporting the notion that for some responses at least the requirement for species-matched CD4 may not be absolute. Evidence for positive selection of mouse T cell receptors in HLA-DR transgenic mice came both from the acquisition of new, HLA-restricted responses to various peptides and from an increased frequency of T cells using the TCR V beta 4 gene segment. An important goal with respect to the analysis of function in HLA transgenic mice is the clarification of mechanisms which underpin the recognition of self-antigens in human autoimmune disease. As a first step towards 'humanized' disease models in HLA transgenic mice, we analyzed the responses of HLA-DR transgenic mice to the human MPB 139-154 peptide which has been implicated as an epitope recognized by T cells of multiple sclerosis patients. We obtained T cell responses to this epitope in transgenic mice but not in nontransgenic controls. This study suggests that HLA transgenic mice will be valuable in the analysis of HLA-restricted T cell epitopes implicated in human disease and possibly in the design of new disease models.

Immunological characterization of hemopoietic cells in the common marmoset, rhesus monkey, and man. In search of a model for human marrow transplantation.

Bone marrow, lymphoid, and peripheral blood cells from the common marmoset and rhesus monkey have been tested with a panel of heterologous and monoclonal antibodies, and their reactivity pattern has been compared with that of blood and bone marrow cells from human donors. Conventional antibodies reveal extensive cross-reactivity within the B cell, T cell, and granulocytic systems in all three species, however, some important differences have been exposed. Only the monoclonal antibodies to HLA-A,B,C and Ia-like antigens react with marmoset cells, and we have exploited this finding to show that the vast majority of colony-forming units (CFU-c) in the marmoset bone marrow (as in man) are Ia positive. The use of the common marmoset as a suitable model for human bone marrow transplantation is discussed in the light of these findings.

The susceptibility of germ-free, oestradiol-treated, mice to Mycoplasma hominis.

Conventionally reared female BALB/c mice, rendered susceptible to Mycoplasma hominis infection of the genital tract by treatment with oestradiol, have increased numbers of endogenous vaginal bacteria. The latter was reflected by the occurrence of bacterial growth in 95 (65.5%) of 145 cultures undertaken to isolate M. hominis from oestradiol-treated mice, but in only seven (4.8%) of 146 cultures from untreated animals. In addition, larger numbers of bacteria were seen in vaginal smears from oestradiol-treated mice than from untreated ones. Furthermore, abscesses developed in the genital region of 27 (17%) of 155 oestradiol-treated mice but in none of 50 that were untreated. However, such proliferation of the endogenous vaginal bacteria was not necessary for colonisation of the vagina by M. hominis. This was determined by showing that six germ-free, oestradiol-treated BALB/c mice given 2.5 x 10(5) ccu of M. hominis intravaginally became colonised vaginally for at least 14 days, with multiplication and spread of the organisms to the upper genital tract and elsewhere, whereas six similar untreated mice given the same inoculum remained uninfected.

Studies of the specificity of ureaplasmas for marmosets.

Marmosets, from which endogenous ureaplasmas had been eradicated by treatment with minocycline, were tested for susceptibility to infection by ureaplasmas from the genital and respiratory tracts of other animal species. They could be infected with ureaplasmas of human and simian origin, but were resistant to bovine and canine ureaplasmas. The results indicated that human, marmoset and squirrel-monkey ureaplasmas may form a biological subgroup, distinct from bovine and canine ureaplasmas, and that host range should not be ignored as a parameter for classification.

Circadian oscillations of body temperature in the marmoset, Callithrix jacchus.

The rectal temperature of 8 marmosets was taken regularly throughout a 76 hour period. A pronounced circadian rhythm was detected: body temperature reached a maximum during the light phase and a minimum during the dark phase.

Breeding nude (nu/nu) mice.

By using as sires homozygous nude males bearing thymus glands from their normal siblings, heterozygous females yield 50 per cent nu/nu offspring under conventional conditions. Most nu/nu females are fertile, but in our experience only 20 per cent of them rear nude litters to weaning age.

The occurrence of ureaplasmas in marmosets.

Ureaplasmas were isolated from the oropharynx of all of 22 male and 19 female adult marmosets and from the genital tract of about a quarter of them. These ureaplasmas seem to be natural inhabitants of the oropharynx and not of human origin because half the animals had had very limited human contact and preliminary serological tests indicate that the organisms are not the same as the known human serotypes. 11 babies born in captivity were found to have oropharyngeal organisms usually within 24 h of birth and the oropharynx of the parents was thought to be the most likely source. The marmoset may be a useful model for studying the role of ureaplasmas in human disease.

The use of a simple barrier system to exclude murine pathogens.

A simple barrier system was used successfully to exclude Mycoplasma pulmonis and Sendai virus from a conventional mouse room. 49 weeks after introduction of the barrier system of management Pasteurella pneumotropica was first isolated from animals in the room.

Vaginal colonization of pig-tailed macaques by Gardnerella vaginalis.

Ten pig-tailed macaques inoculated intravaginally with Gardnerella vaginalis organisms were colonized for 11-39 days. In contrast, 4 tamarins and 3 chimpanzees inoculated similarly failed to become colonized. Examination of Gram-stained vaginal smears obtained from infected pig-tailed macaques failed to demonstrate clue cells, a feature which is pathognomonic of non-specific vaginitis in humans. Additionally, the pH value, the levels of non-volatile fatty acids and the anaerobic flora of the macaque vagina differed from these aspects of the human vagina. While these differences indicate that gardnerella-infected macaques are unsuitable as a model of gardnerella-associated vaginitis in humans, such animals may prove useful for studying selected aspects of the biology of G. vaginalis such as the adhesion and interaction of the bacteria with the vaginal mucosa.

The antifertility activity of 2-(isopropylamino) ethanol in the mouse.

Intraperitoneal administration of 2-(isopropylamino) ethanol on the 3rd day of pregnancy reduces the extent of the decidual cell reaction induced by the blastocyst and can cause the death of the conceptus by the 6th day of pregnancy. Evidence is presented to support the theory that the compound administered in this way has a direct effect on the conceptus.

Placental and foetal weight in the nude mouse.

Placental and foetal weight and litter size were studied on the 18th day of pregnancy in the athymic nude mouse. Placental weight and litter size were unaffected by the absence of a thymus. Foetal weight was reduced, probably as a result of the health status of such animals.

Absence of effect of maternal immunization to paternal antigens on placental weight, fetal weight and litter size in the mouse.

No evidence was obtained that immunization to paternal antigens affected placental weight, fetal weight or litter size on Day 18 of pregnancy in female mice.

Effect of tolerance to paternal antigens on placental and fetal weight in the mouse.

Placental and fetal weight was measured on the 16th day of pregnancy in normal and tolerant mice. Placental weight was increased in A mice tolerant to C57BL/10 mice only when donor cells from males were used. Fetal weight was unaffected.

Establishment of functional T cells in SCID mice does not lead to termination of pregnancy.

Syngeneic (CB20) thymus and spleen T cells transferred to SCID mice, and shown to be present by flow cytometric analysis and functional by their ability to reject third-party skin grafts, do not lead to a detectable failure of syngeneic or allogeneic pregnancy. Unless the small number of B cells contaminating the T-cell innocula are capable of mounting a blocking antibody response, it is concluded that these results show that a humoral ('blocking antibody') response is not essential for successful pregnancy.

The effect of pregnancy on lymph node weight in the mouse.

Lumbar and renal lymph nodes, inguinal lymph nodes and spleen weights were recorded during pregnancy in mice after mating with males of the same (syngeneic) or a different (allogeneic) strain. The weights of these nodes increased during pregnancy. Spleen weights increased up to the fifteenth day of pregnancy and then decreased in weight. There was no consistent correlation of any of these measurements with the extent of the antigenic dissimilarity between mother and conceptus.

The effect of fostering nude mice with allogeneic mothers on subsequent mortality.

Mortality in nude mice fostered by allogeneic mothers was studied. The data failed to support the hypothesis that mortality was due to graft versus host disease resulting from the passage of immunocomponent cells to the young in the mothers' milk. It was apparent that there were significant differences in the ability of mothers of different strains to rear nude mice.