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Monokine induced by IFN-gamma (MIG; CXC chemokine ligand (CXCL)9) is important in T lymphocyte recruitment in organ transplantation. MIG/CXCL9 stimulate CD4 lymphocyte proliferation in a MHC class II-mismatched MLR and also increased the number of IFN-gamma-producing CD4 lymphocytes in ELISPOT. Neutralization of MIG/CXCL9 in MLR reduced T lymphocyte proliferation, IFN-gamma-inducible protein 10/CXCL10 and IFN-inducible T cell alpha chemoattractant/CXCL11 had similar effects on T lymphocyte proliferation. MIG/CXCL9 stimulated T lymphocyte proliferation in MHC class I and total MHC-mismatched MLRs. Neutralization of CXCR3 reduced MIG/CXCL9-induced T lymphocyte proliferation and the number of IFN-gamma-positive spots on ELISPOT. The proliferative effects of MIG/CXCL9 were mediated via an IL-2-independent pathway and were controlled by IFN-gamma.