The role of CD8+ cells in the establishment and maintenance of a Trichuris muris infection.

Chronic infection by the caecal-dwelling intestinal murine nematode Trichuris muris occurs if given as a high-dose infection to 'susceptible' AKR mice or as a low-dose infection to the normally 'resistant' C57BL/6 mouse strain. Both regimes result in a type 1 cytokine response, i.e. high levels of IFN-gamma and IL-12. Here we show this susceptible response is associated with a large population of CD8(+) IFN-gamma(+) cells within the mesenteric lymph nodes and numerous CD8(+) cells infiltrating the caecal mucosa. Despite this, the in vivo abolition of CD8(+) cells within AKR and C57BL/6 mice, either prior to infection or once infection has become established, failed to affect chronicity, implying that CD8(+) T cells are not essential for the initiation or maintenance of the susceptible response to T. muris. Interestingly, the percentage of IFN-gamma(+) CD4(+) cells increased in treated groups, perhaps in a compensatory role. The majority of antigen-specific cytokine responses were comparable in both treated and control groups, although IL-5 was fivefold higher in animals receiving anti-CD8 mAbs and IFN-gamma was also raised in treated mice. Mastocytosis was unaltered by CD8 depletion, however, paradoxically, eosinophilia within the caecum was reduced in treated mice. Together these data clearly demonstrate that CD8(+) T cells are associated with chronic T. muris infection; however, these cells are dispensable for both the early and late phases of this response, but do appear to play a role in the regulation of certain cytokines and caecal eosinophilia.

There is an increase in expression of the cytotoxic T-lymphocyte antigen-2 alpha gene during pregnancy.

OBJECTIVE: Our purpose was to identify genes that exhibit increased expression in the uterus during pregnancy. STUDY DESIGN: A differential screen was performed against a pregnant mouse uterus complementary deoxyribonucleic acid library by use of probes derived from pregnant and nonpregnant uterus. Multiple clones related to the cytotoxic T-lymphocyte antigen-2 alpha gene were isolated. RESULTS: Northern hybridization disclosed that message is present in both the gravid and nongravid uterus, but there is a substantial increase in expression during pregnancy. Expression is not found in a variety of other fetal and adult tissues evaluated (excluding placenta). CONCLUSION: The uterus (or cells present within the uterus) constitutes a major site of in vivo expression for the cytotoxic T-lymphocyte antigen-2 alpha gene, and expression of this gene is increased during pregnancy.

An increase in expression of the lipocalin 24p3 is found in mouse uterus coincident with birth.

OBJECTIVE: To provide novel insights into the molecular events associated with parturition, a differential screen was made of a mouse uterine complementary deoxyribonucleic acid library to identify selectively expressed genes in late pregnancy. STUDY DESIGN: A differential hybridization was used to screen a mouse complementary deoxyribonucleic acid library prepared from late pregnancy uterus. A 1 kb clone was isolated that was subsequently identified as 24p3, a member of the lipocalin family. By use of radiolabeled complementary deoxyribonucleic acid probes prepared from this clone Northern hybridizations were conducted against total ribonucleic acid purified from mouse uterus collected during late pregnancy and the first week after birth and a variety of other mouse tissues to determine whether this gene is selectively expressed in the uterus coincident with parturition. RESULTS: Low levels of message for the 24p3 gene could be detected in uterine ribonucleic acid, but there was a massive increase in the level of message for this gene on the days surrounding birth. Northern hybridizations conducted against additional tissues collected from both pregnant and nonpregnant mice did not detect message to a similar degree as found in the uterus. CONCLUSIONS: The uterus constitutes a major site of expression of this gene, particularly near birth. The expression of this gene coincident with birth suggests a potential physiologic role of the neutrophil with the induction of labor.

Selenoprotein P expression in liver, uterus and placenta during late pregnancy.

To identify genes that exhibit increased expression in the placenta during late pregnancy, the technique of differential cDNA library screening was used to isolate a clone subsequently identified as the 3' untranslated region of the mouse selenoprotein p gene. Random primed radiolabelled cDNA probes were constructed from this clone and these probes were used to conduct Northern hybridizations against total RNA purified from mouse placenta, liver (maternal and fetal) and uterus collected sequentially during the latter third of pregnancy. Signal is present in the placenta and beginning 4 days before birth, the level of message increases, reaching maximal levels at term. The level of expression in the placenta at maximum is approximately 25 per cent of that observed in adult liver. In liver obtained from pregnant females, the level of message is increased compared to nonpregnant adults, but returns to normal shortly after birth. Message is also found in the fetal liver beginning at 4 days before birth and exhibits a pattern of expression similar to the placenta. The similarity of expression observed in fetal liver and placenta suggests a coordinated regulation of expression of this gene in these tissues. There is a minimal amount of signal present in the uterus and the expression does not appear to vary. We speculate that selenoprotein p may play a role in the transplacental transport of selenium to the fetus during late pregnancy.

Transferrin gene expression in maternal liver, fetal liver and placenta during pregnancy in the mouse.

Two clones that are homologous to the mouse liver transferrin gene were isolated from a differential screen performed on a mouse cDNA library constructed from placenta. Using an insert derived from the larger of these clones as a template for the generation of random primed cDNA probes, northern blots were conducted against total RNA collected sequentially from placenta (7 days before birth to birth), maternal liver (7 days before birth to birth) and fetal liver (5 days before birth to birth). An approximately 2.3 kb message was detected in all three tissues which was upregulated in late gestation. Message was very abundant in both maternal and fetal liver, and present, but weak, in placenta. The clones were partially sequenced and both clones contain sequence that is identical to mouse liver transferrin. The data presented demonstrate an increase in mRNA transferrin in late gestation in maternal and fetal liver. Additionally, the placenta expresses a gene homologous to liver transferrin and it also is upregulated in late gestation.

Kidney androgen-regulated protein gene is expressed in the uterus during late pregnancy.

Kidney androgen-regulated protein (KAP) is a unique protein of unknown function that is transcriptionally induced by sex steroids. KAP is thought to be predominantly a kidney-specific gene. After conducting a differential screen of a mouse uterus cDNA library, a clone was identified that is identical to KAP. Using this cDNA to generate radiolabeled cRNA probes, Northern blots were conducted against the following tissues collected sequentially during the latter third of pregnancy: kidney, uterus and placenta. Abundant message was present in all samples of the kidney tested and there was a slight, but apparent, increase (1.5-fold) in expression during the period surrounding birth. Message is also present in the uterus, at levels comparable to the kidney, but expression occurs only during the period surrounding birth. Message is not present in the uterus at any other time. Message is also not detected in the placenta or in several other tissues tested. In addition to the kidney, KAP gene is also transcribed at equivalent levels in the uterus. Unlike the kidney, expression in the uterus is limited to the perinatal period.