Lymphocyte migration across major histocompatibility barriers in splenectomized rats.

Localisation and migration patterns of iv injected radio-labelled thoracic duct (TD) lymphocytes were studied in particular with regard to passage through lymph nodes and re-entry into thoracic duct lymph. To avoid unwanted splenic sequestration of migrating lymphocytes presenting alloantigens to the recipient, only splenectomized recipients were used. Donor cells and recipients differed at the MHC (RT-1) locus, either in fully allogeneic (AO -- greater than BN and v.v.) or semi-allogeneic (AO -- greater than AO X BN and v.v.) combinations. In two of these combinations (BN -- greater than AO and AO X BN -- greater than AO) deficient output in TD lymph correlated with deficient localisation in lymph nodes and high amounts of radioactivity in the liver. In the other allogeneic combination (AO -- greater than BN), however, high TD output (i.e. when compared with the syngeneic combination BN -- greater than BN) correlated with good localisation in lymph nodes and low (control) levels of radioactivity in the liver. It was postulated that lymphocyte migration from blood to lymph under these circumstances can only be studied as an artifact secondary to whether or not migrating cells are removed from the circulation before they can reach and cross HEV's. These Allogeneic (or Altered) Lymphocytes Removing Tissues (by definition: Extranodular) may (conceptually) be comprised within one system: ALERT. It is our working hypothesis that the study of lymphocyte migration across (major) histocompatibility barriers is seriously impaired by the functioning of ALERT. It might be worthwhile to try and create conditions in which interference by this system is prevented, e.g. by using tolerant animals or bone-marrow chimeras.