Tolerance in early embryo aggregation-derived mouse chimaeras

The Use of Early Embryo Aggregation Derived Chimaeras. I. To Study Immunological Tolerance*

“…Although there is often a change in the proportion of the two parental cell populations this is generally relatively minor (Mintz & Palm, 1969) and there is no evidence to date to suggest that with the exception of NZB chimaeras that this is due to a breakdown in tolerance. Indeed in a group of AKRttCBA/H-T6 chimaera where the change in proportion of the two parental cell populations was profound (Ford et a/., 1974;Barnes et a/., 1974a), there was no evidence of GVH activity at least as determined in the local popliteal lymph node weight gain assay (Barnes & Graham, 1975). This assay was originally described by Ford and his colleagues (Ford et a/., 1970) for use in the rat and was subsequently adapted by us for use in the mouse (Twist & .…”

“…Clearly the chimaeras' lymphoid cells appear totally unreactive compared with the controls. The results summarized in Tables 1 and 2 are detailed in full elsewhere (Barnes & Graham, 1975;Festenstein et.uZ., 1975) with other relevant controls (Twist & . Results were clear cut, chimaera cells do not react in uivo against F1 recipients, at least in the local popliteal lymph node weight gain assay.…”

Chimeric drift and immunological tolerance in allophenic mice

“…Neither stable nor unstable allophenic mice have detect able serum blocking activity as determined by antibody mediated cytotoxi city testing. This observation is consistent with the results of other workers (Meo et al, 1973;Festenstein et al, 1975;von Boehmer et al, 1975a;Barnes and Graham, 1976) who similarly have failed to detect serum blocking activlEy Oif suppressor' cells in allophenic mice. Thus, the overall picture that emerges from these observations is that chimeric drift in the two cell populations is probably the response of two independent control mechanisms and the mechanisms involved are not the same as those responsibile for maintenance of tolerance.…”

The Use of Early Embryo Aggregation Derived Mouse Chimaeras. Iii. A Tool of Immunogenetics*

“…Tolerance in EEA chimaeras-a subject of much past controversy is now considered to be due to heterogeneous clonal elimination. Heterogeneous in so far as that elimination is confined to potentially autoreactive cells capable of H H self ~) t self reactivity leaving other 'non-fatal' lymphoid cell populations such as those involved in mixed lymphocyte reactivity, allotype production, PHA response etc., intact (Festenstein et al, 1975;Barnes, 1976aBarnes, , 1976cBarnes, , 1976d. One aspect concerning basic immunogenetics and possibly tolerance is that it is not infrequent to note a change in the proportion of the two parental cell populations during life of the EEA derived chimaera.…”

“…(iii) Allotype suppression was investigated in a group of seven EEA BALB/c t ) C57/B1 chimaeras. These chimaeras were primarily investigated in respect of the mechanism of tolerance (Festenstein et al, 1975;Barnes, 1976aBarnes, , 1976cBarnes, , 1976d. These chimaeras were derived fom BALB/c mothers pre-immunized and producing high titres of anti-lgG C57/B1 allotype.…”