Activation of T lymphocytes to M locus determinants in vivo. I. Quantitation of T cell proliferation and migration into thoracic duct lymph.

Proliferative responses to M locus (Mls) determinants were investigated in vivo by injecting T cell-containing populations intravenously into irradiated H2-identical, Mls-incompatible mice. Responses were studied 1-6 days later by measuring levels of radioactivity in the spleen and lymph nodes of the recipient 45 min after intravenous injection of tritiated thymidine. High responses were observed against Mlsa and Mlsd determinants, i.e. determinants which give strong proliferative responses in vitro. With injection of thoracic duct lymphocytes (TDL), lymph node or thymus cells, the responses, both in the spleen and the lymph nodes, reached a peak at day 3-4 and then fell sharply. This was in marked contrast to the stimulation observed with H-2-incompatible mice where, with TDL or lymph node cells (though not with thymus cells), responses were low at day 3-4 but reached high levels at day 6. Significant responses were also observed against Mlsb and Mlsc determinants, i.e. determinants which stimulate poorly in vitro. The kinetics of this response differed from that against Mlsa or Mlsd determinants in in that proliferation was very low at day 4 but high at day 6. No evidence was found that the responses observed reflected "back-stimulation" by the host. Since congenic resistant strains were not used, the possibility that the stimulation observed was in fact due to minor transplantation antigens rather than Mls determinants could not be excluded. Large numbers of blast cells appeared in thoracic duct lymph of mice sustaining responses to Mlsa or Mlsd determinants. Nearly all of these cells had recently synthesized DNA and entered the lymph after day 3.