An ongoing in vivo immune response affects the abundancy and differentiation of lymphokine-activated killer cell precursors, but does not influence their broad spectrum target reactivity

Using a model of local lymph node (LN) immunization, we investigated the effect of in vivo Ir on the generation of lymphokine-activated killer (LAK) cells or their precursors. Ag used for immunization were SRBC, horse RBC, OVA, keyhole limpet hemocyanin, or CFA. Ag-draining LN, in the acute phase of the Ir, did not contain detectable LAK effector activity, nor an enhanced NK activity. After culture for 3 to 5 days in the absence of exogenously added IL-2, immunized LN cells developed a spontaneous LAK-like cytotoxicity. This activity represented a substantial fraction of the IL-2-generated LAK cytolysis and was mediated by a Thy-1+ cell population phenotypically indistinct from IL-2-induced LAK. Inclusion (on day 0 of culture) of antibodies to IL-2, IL-2R, IL-4, IL-6, IFN-gamma, or TNF suggests a marginal involvement of IL-2 and IL-4 in the generation of this response. LAK, induced in vitro by exogenously added IL-2, developed earlier in LN cells immunized with particle Ag (SRBC, horse RBC, and CFA), but not with protein Ag (OVA and keyhole limpet hemocyanin). This effect was not mediated by endogenous IL-4. During further culture time in the presence of a saturating IL-2 concentration, similar levels of LAK activity were generated in naive and immunized LN cells. This agrees with the similar or slightly higher LAK precursor frequencies in immunized versus naive LN as assessed by limiting dilution experiments. Considering the 2.7-fold to 18-fold increase in cell content of the immunized LN, due to a recruitment and expansion of Ag-reactive B and T lymphocytes, a de novo generation of LAK precursors at the site of the Ir, and resulting from the Ir, must be assumed. In conclusion, our results suggest an interrelation between immune reactivity and LAK responses.