MECHANISM FOR MACROPHAGE ACTIVATION AGAINST CORYNEBACTERIUM-PARVUM - PARTICIPATION OF T-CELLS AND ITS LYMPHOKINES

It is well known that corynebacterium parvum activates macrophages to produce tumor necrosis factor (TNF). It is suspected that the activati on of macrophages by C. parvum requires T-cell participation. The purp ose of this study was to confirm that T cells participate in the activ ation of macrophages by C. parvum. TNF production in vitro from the sp leen cells of BALB/c- +/+ mice was abrogated completely by the pre-tre atment of spleen cells with anti-Ia antiserum and complement, indicati ng that Ia(+) cells are the source of TNF. TNF production was not elic ited at all in BALB/c-nu/nu mice. However, there was an increase in th e number of Ia(+) cells as well as an increase in the weight of spleen and liver. Supernatant from a culture of spleen cells stimulated with phytohemagglutinin-P (a PHA-induced lymphokine) made it possible for BALB/c-nu/nu mice to produce TNF, associated with an induction of Lyt- 1(+) cells and Lyt-2(+) cells. However, treatment with the lymphokine did not augment the increases of Ia(+) cells or liver and spleen weigh ts. These results suggest that increasing the number of Ia(+) cells is not sufficient to bring about TNF production; Ia(+) cells must also b e stimulated by T cells or T-cell lymphokines in order to produce TNF. These results suggest that T cells play an essential role in the acti vation of Ia(+) cells against C. parvum.