MODULATION OF MURINE CYTOKINE RESPONSES TO MYCOBACTERIAL ANTIGENS BY HELMINTH-INDUCED T-HELPER-2 CELL RESPONSES

BALB/c mice inoculated with live Brugia malayi microfilariae (mf), or immunized with a soluble filarial extract (B. malayi Ag (BmA)), develo p a pronounced Th2-like response over time. In contrast, single or rep eated immunizations with a soluble Mycobacterium tuberculosis Ag prepa ration (purified protein derivative, PPD) stimulates a Th1, but not Th 2 response (IFN-gamma >> IL-4, IL-5). To determine if the Th1 response to PPD can be modulated by the ongoing helminth-induced Th2 activity, mice were: 1) immunized simultaneously with BmA and PPD; 2) immunized first with BmA, then with PPD; or 3) inoculated with live mf and immu nized with PPD at various times thereafter. Simultaneous immunization with both Ag had no effect on the Th response induced by PPD, i.e., it was strictly Th1. In contrast, establishment of a Th2 response by eit her inoculation of live mf or immunization with BmA before administrat ion of PPD skewed the PPD-specific Th response such that IL-4 and IL-5 were produced in addition to IFN-gamma. IL-4 and IL-5 levels produced in response to PPD under these conditions were further elevated in vi tro in the presence of neutralizing IFN-gamma. Finally, in vivo neutra lization of IL-4 diminished induction of Th2 responses to PPD. These r esults demonstrate that ongoing Th2 responses to helminth Ag modulate the Th response to mycobacterial Ag by an IL-4 dependent mechanism.