SummaryThe differentiation potential of putative intermediates between CD4 + 8 + thymocytes and mature T cells has been examined. Such intermediate populations were sorted, in parallel with CD4 § 8 + thymocytes, from three types of C57BL/6 mice: major histocompatibility complex (MHC) class II-deficient mice, mice transgenic for an o~/~ T cell receptor (TCR) restricted by class I MHC and normal mice. The sorted populations were then transferred into the thymus of nonirradiated C57BL/Ka mice differing in Thy 1 allotype, and the progeny of the transferred cells were analyzed 2 d later. Surprisingly, with all three types of donor mice, a major proportion of the CD4 + 8~'TCRint-derived progeny were found to be CD4-8 + TCR ~ cells, thus delineating a new alternative pathway for development of the CD8 lineage. In contrast, the transfer of CD4int8 + TCR int thymocytes produced CD4-8 + TCR hi cells but no significant proportion of CD4+8-TCR hi cells, suggesting that there is no equivalent alternative pathway for the CD4 lineage. The results negate some of the evidence for a stochastic/selective model of lineage commitment, and point to an asymmetry in the steps leading to CD4-8 § versus CD4 + 8-T cells.M ature T lymphocytes can be divided into two subpopulations based on their expression of the coreceptor molecules CD4 and CD8. Both populations recognize antigens in the form of peptides presented by MHC molecules. In general, CD4-8 + T cells recognize antigens presented on class I MHC, whereas CD4 + 8-T cells recognize antigens presented on class II MHC. This recognition process involves both an antigen-specific interaction between the TCR and the peptide-MHC complex (1) and an interaction between the coreceptor, either CD4 or CD8, and a conserved region of the same MHC molecule, class II or class I, respectively (for a review see reference 2).Both CD4-8 + and CD4+8 -T cells develop within the thymus from a common CD4 + 8 + TCR 1~ cortical thymocyte population, which itself arises by a developmental process involving successive rearrangements of TCtL c~ and/3 genes (for reviews see references 3 and 4). CD4 + 8 +TCR l~ thymocytes appear destined to die unless they receive a selective set of signals that involve interaction of the TCR and either CD4 or CD8 with peptide-MHC complexes expressed by the thymic stroma. The overall result is the upregulation of TCR, the downregulation of either CD4 or CD8, and the rescue of the celt from programmed death. The entire process, which dictates the antigen specificity and the MHC restriction of the emerging T cell populations, is termed positive selection (5).The precise sequence of events that occurs during positive selection has not been elucidated, but two different models, known as the "instructive" and the "stochastic/selective" models, have dominated the discussion about mechanisms of positive selection. In the instructive model, engagement of MHC class I gives the uncommitted CD4 § 8 + thymocyte a positive selection signal that at the same time also instructs the thymocyte to ...

The aim of the present study was to investigate the effect of feeding strategy on the performance of oral stereotypies, such as tongue-rolling and bar-biting, and other behaviours in lactating dairy cows. Thirty–seven cows of the Swedish Red and Wliite breed were randomly assigned into three treatments with different feeding strategies. Cows in treatment (AL) were given food ad libitum during the whole experimental period, which lasted from weeks 3 to 26 post partum. The second group (AL–R) was given food ad libitum during weeks 3 to 14 post partum, thereafter they were given food at a restricted level. The third group (R) was given food at a restricted level during the whole experiment period. All cows were offered a total mixed ration consisting of 650 g concentrate and 350 g forage per kg twice a day and their individual daily food intakes were registered. Behavioural recordings were made for 4 h on a fixed day every 2nd week, where each individual cow was observed every 2nd minute.During the complete experimental period, 27 out of the 37 cows showed stereotypies; 13 cows in group R, 10 in group AL–R and four in the AL group. The proportions of cows showing stereotypies were not independent of feeding treatment within the respective periods (P < 0·01). The stereotypy levels, counted as the mean frequency of recordings per treatment period, increased significantly between period 1 (lactation weeks 3 to 14) and period 2 (weeks 17 to 26) in group AL–R (P < 0·01) and in group R(P < 0·01), but not in the AL group. In period 2 the R cows had significantly higher stereotypy levels than the cows in the AL–R group (P < 0·01). Group R decreased the time spent eating between the periods (P < 0·001), with the same tendency in group AL–R. The AL group had longer eating time in period 2 than the AL–R (P < 0–001) and the R (P < 0·001) cows. The AL cows had a higher frequency of rumination than the other treatments in period 2 (P < 0·01). Both the AL–R and the R cows increased their activity levels between the periods (P < 0·001 for both). There were also differences between treatments in period 2, where the AL cows were less active than the AL–R (P < 0·05) and the R cows (P < 0·01).It is concluded that oral stereotypies in dairy cows are highly affected by feeding strategy, where restrictive feeding of a mixed food induces significant increases of stereotypies. The results of this investigation clearly indicate that restricted feeding of a diet with high levels of concentrate has a negative effect on the well being of lactating cows.

SlLlmmal'yTo determine the developmental stages at which positive selection can act to produce mature T cells, CD4 + 8 § 31~ thymocytes of large dividing type and of small nondividing type were sorted and transferred into the thymus of nonirradiated Thy-1 congenic recipient mice. In contrast to earlier studies, the small as well as the large thymocytes produced mature CD4+8-3 hi and CD4-8+3 hi progeny, although production was less efficient from the small cells. The relative efficiency of small cells was increased and was close to that of large cells when bcl-2/anti-HY T cell receptor (TCR) c~ transgenic donors were used to improve cell survival, overcome stress effects of the transfer process, and increase the frequency of selectable cells. The results from transferring small CD4+8+3 l~ thymocytes expressing a TCR transgene from a nonselecting to a selecting thymic MHC environment also confirmed that the small cells were capable of being selected and maturing. Thus the developmental window available for positive selection includes the small CD4 § 8 + 31~ thymocytes. The results also showed a striking difference in the kinetics of production of mature progeny from the transferred CD4 + 8 + 31~ precursors. CD4 + 8-3 hi cells appeared several days before CD4-8 § 3 hi cells, apparently because the CD4-8 + lineage cells spent several days in transit as CD4 + 8 + 3 hi intermediates before losing CD4. Most CD4 § 8-lineage cells on the other hand, either passed very rapidly through this intermediate stage, or lost CD8 before increasing the expression of CD3.

Clophen A50, a technical preparation of polychlorinated biphenyls (PCBs), was separated into four fractions; three containing chlorobiphenyls with 0, 1, or 2 to 4 ortho chlorines and one containing di- and tricyclic impurities such as naphthalenes and dibenzofurans. Clophen A50, the four fractions, and a synthetic mixture of the biologically most active non-ortho-chlorinated congeners (3,3',4,4'-tetra-, 3,3',4,4',5-penta-, and 3,3',4,4',5,5'-hexachlorobiphenyl), were separately mixed in the feed and given to female mink during the reproductive season. The concentration of a given compound in the feed mixture was equivalent to its concentration in the feed mixed with Clophen A50. Hepatic 7-ethoxyresorufin O-deethylase (EROD) activity in adults was enhanced 2-3 times by Clophen A50, the fractions containing non- or mono-ortho-chlorinated congeners, and the synthetic mixture. In neonatal kits delivered by females treated with non- or mono-ortho-chlorinated congeners, EROD was enhanced to about 30 times the control value. No live kits were delivered by the females treated with unfractionated Clophen A50. The fractions containing congeners with two to four ortho chlorines or di- and tricyclic compounds did not significantly induce EROD in either adults or kits. Clophen A50 reduced hepatic and pulmonary vitamin A contents in adult mink, while renal vitamin A was unaffected. Responses to the fractions containing the non- and mono-ortho-chlorinated congeners were similar to those obtained with Clophen A50. Their effects were, however, less pronounced, particularly with respect to the hepatic vitamin A reduction. The fractions containing congeners with two to four ortho chlorines and the di- and tricyclic compounds had no significant effects on tissue vitamin A contents.(ABSTRACT TRUNCATED AT 250 WORDS)

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