Interleukin-7 has demonstrated potent enhancing effects on the growth and differentiation of several immature cell types, including thymocytes, and on survival of resting and antigen activated T cells. In this study, we evaluated the effects of IL-7 on post-thymic antigen-specific T cells from human blood. IL-7 was found to enhance proliferation responses and IFN-gamma secretion of myelin or recall Ag-specific Th1 cells through the selective up-regulation of the IL-2R alpha and gamma but not beta chains in both an Ag-dependent and Ag-independent manner, but did not affect monocytes, B cells, or NK cells. These functions of IL-7 enhanced the detection of Th1 but not Th2 cell frequency by > 2.5 fold, and promoted selection of kg-specific Th1 cells by the limiting dilution method. Moreover, IL-7 pretreatment conferred increased resistance of CD4 + T cells to CD8 + cell lysis, These studies demonstrate that IL-7 promotes the growth and survival of circulating Ag-specific human Th1 cells through a mechanism that probably involves the gamma c common receptor for IL-2 family members that includes IL-7. (C) 1999 Elsevier Science B.V. All rights reserved.