Conversion of specific to nonspecific cytotoxic T lymphocytes.

The type of cytotoxic T lymphocyte (CTL) generated during a mixed leukocyte culture has been shown to depend on the purity of interleukin 2 (IL 2) used to stimulate growth. Antigen-specific CTL requiring both antigen and IL 2 to proliferate or express cytotoxicity (designated Type I in this work) are generated and maintained with highly purified IL 2. In the presence of IL 2 alone, they persist in a quiescent, noncytotoxic state, and on its removal they rapidly die. A second type of CTL (Type II), of nonspecific cytotoxicity, and dependent only on IL 2 for growth, is generated by exposure to an impure lymphokine preparation containing IL 2. Type I cells are T lymphocytes which are nongranular and nonadherent, whereas Type II cells are larger, adhere to plastic, and contain many granules. Cloned Type I cells are converted to Type II under three conditions: by low levels of IL 2 in the presence of a crude lymphokine preparation; by high levels of IL 2 in the presence of antigen; or by high levels of IL 2 in the presence of the phorbol diester PMA. Conversion results from an effect of the growth conditions on individual cells, and not from selection of a minor population.