1. Transfer of spleen cell suspensions from normal neonatal donor NIH mice into newborn recipient NIH mice injected with Shigella soluble antigen (SSA) prevents the establishment of immunologic unresponsiveness to Shigella.

  2. The optimal time interval between injection of cell suspension and antigen for maximum interference of tolerance was found to be less than 48 hr after birth. Transfer of cells 4 to 7 days after neonatal injection of antigen resulted in partial interference. Transfer of cells 14 days or longer after birth had no detectable effect.

  3. Transfer of large numbers of spleen cell suspensions was found to be more effective in interfering with tolerance than transfer of smaller numbers of cells.

  4. Intravenous and intraperitoneal administration of cell suspensions were found to be the most effective routes for preventing tolerance induced by the i.p. injection of Shigella antigen.

  5. Transfer of lymph node cell suspensions was nearly as effective as transfer of spleen cell suspensions. Thymus cells were also capable of preventing tolerance, but were not as effective as spleen cells. Transfer of peritoneal exudate cells was much less effective, whereas buffy coat leukocytes and bone marrow cells were essentially negative.

  6. Injection of larger concentrations of Shigella antigen necessitated transfer of larger numbers of spleen cells for comparable interference of tolerance.

  7. Transfer of spleen cells from young mice, 1 to 21 days of age, which were themselves tolerant to Shigella following injection of SSA at birth, to other newborn mice receiving SSA also resulted in prevention of tolerance.

  8. These observations suggest that transfer of various lymphoid cell suspensions into SSA-injected newborn mice may interfere with establishment of unresponsiveness by increasing the ratio of available lymphoid cells to antigen, and thus reduce the concentration of SSA per cell below a postulated threshold level necessary for establishing and maintaining tolerance.

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