Trachoma, caused by the obligate intracellular organism Chlamydia trachomatis, is the world's leading cause of preventable blindness for which a vaccine is needed. We have previously shown that a plasmid-deficient live-attenuated trachoma vaccine delivered ocularly to macaques elicited either solid or partial protective immunity against a virulent ocular challenge. Solidly protected macaques shared the same MHC class II alleles implicating CD4(+) T cells in superior protective immunity. Understandably, we sought to define T cell immune correlates in these animals to potentially improve vaccine efficacy. In this study, following a 2-y resting period, these macaques were boosted i.m. with the live-attenuated trachoma vaccine and their peripheral T cell anamnestic responses studied. Both solidly and partially protected macaques exhibited a CD4(+) and CD8(+) T cell anamnestic response following booster immunization. CD8(+) but not CD4(+) T cells from solidly protected macaques proliferated against soluble chlamydial Ag. We observed a more rapid T cell inflammatory cytokine response in tears of solidly protected animals following ocular rechallenge. Most notably, depletion of CD8(+) T cells in solidly protected macaques completely abrogated protective immunity. Collectively, our findings support the conclusion that CD8(+) T cells play an important but unexpected role in live-attenuated trachoma vaccine-mediated protective immunity.