Indirect evidence suggesting a link between immune function and mood disorders is supported by the anxiety-like behaviour that is characteristic of recombination-activating gene 1 (Rag1)−/− mice. This study showed that the presence of CD4+ T cells but not of CD8+ T cells in Rag1−/− OT-II-transgenic mice but not in Rag1−/− OT-I-transgenic mice reverts the increased digging and marble-burying behaviours of Rag1−/− mice. Transient depletion or reconstitution of CD4+ or CD8+ T cells did not affect these activites, which indicates that life-long immunodeficient conditions are required to affect behaviour. There were no differences in systemic factors or in brain anatomy that could be an explanation for the altered emotional behaviour. Whole-brain microarray analysis showed that Rag1−/− OT-II mice have a genetic fingerprint more similar to wild-type mice than to Rag1−/− mice. Nine main signalling pathways (including genes involved in various neuropsychological conditions) were significantly altered in Rag1−/− mice compared with wild-type mice.