The popliteal lymph node response to streptozotocin is under type 1, MHC class-I restricted, CD8(+) T-cell control

The popliteal lymph node (PLN) assay has been proposed to predict the 'auto immunogenic' potential of xenobiotics. A better understanding of the proces ses involved in PLN responses is needed to establish the value of this assa y for preclinical safety evaluation. In order to determine whether PLN resp onses involve CD4(+) or CD8(+) T-cells, the effects of streptozotocin (STZ) , a prototypic immunotoxic compound, were analyzed after injection into the hind footpad of C57 BL/6 mice and major histocompatibility complex (MHC) c lass I or II deficient mice. The involvement of type 1 or. type 2 cell cont rol on the production of cytokine mRNAs was analyzed in lymph node cells by quantitative RT-PCR, together with the analysis of a wide range of cytokin e mRNAs after STZ injection (IL-1 alpha, IL-1 beta, TNF-alpha, IFN-gamma. I L-2, IL-2 receptor, IL-4, IL-5, IL-6, IL-IO and IL-12). We have found that mice depleted in CD8(+) T-cells did not respond to STZ, whereas mice deplet ed in CD4(+) T-cells exhibited the expected positive PLN responses, with in creased weight and cellularity indices. STZ induced a low production of int erleukin (IL)-2 mRNAs, a mild increase in IL-1 alpha and IL-beta mRNAs prod uction, and a dramatic increase in IFN-gamma, IL-I beta, TNF-alpha, IL-12 a nd IL-2 receptor mRNAs, which correlated with positive PLN responses. No ef fects on IL-4, IL-5 and IL-IO mRNAs synthesis were noted. In CD8(+) T-cell deficient mice, there was no production of IFN-gamma or IL-6 mRNAs. These r esults suggest that PLN responses to STZ are under the control of type 1, M HC class-I-restricted, CD8(+) T-cells. This is in accordance to the known p hysiopathology of STZ-induced diabetes. Additional studies are necessary to establish the mechanism of CD8+ T-cell activation. (C) 2000 Elsevier Scien ce Ireland Ltd. All rights reserved.