Maturation of thymus-dependent lymphocytes after confrontation with histo-incompatible cells

Antigen-induced differentiation of mature T lymphocytes after in vitro exposure to transplantation antigens has been reviewed. Upon confrontation with histo-incompatible cells the resting alloantigen-reactive T lymphocytes transform into blasts and divide several times. Concomitantly they acquire the capacity to kill relevant allogeneic target cells. Generation of killer cells requires DNA synthesis and cell division. It is also evident that at least two subsets of T cells participate in the generation of T killer cells. In vivo studies suggest that the activated T cells cooperate with B cells, and that this cooperation is necessary in IgG class alloantibody response. Other studies, performed in vitro, have demonstrated that the alloantigen-activated lymphocytes may also have an immulogically specific suppressive effect on an alloimmune response. At any rate, after the cell proliferation ceases, the T blasts return to resting state and revert back into small lymphocytes. The "secondary" T memory lymphocytes are restricted to the antigens of the first confrontation. Second stimulation by the original histocompatible (but not by unrelated) cells leads to a characteristic prompt secondary proliferative and cytotoxic response. The memory T lymphocytes do not respond to the T mitogens (PHA and ConA) but do respond to relevant histo-incompatible membrane preparations and to relevant UV-killed stimulator cells (non-primed T lymphocytes are unalbe to do so). Cell division is not absolutely necessary for the generation of killer cells in the anamnestic secondary response. The memory T lymphocytes are long-lived and are recovered up to 20 weeks after parking to T-deprived syngeneic hosts. While resting in the syngeneic host they grandually lose the ability to respond promptly, indicating that T-cell memory on the cellular level is limited.