Objective T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Serum‐derived exosomes are increased in SLE patients and are correlated with disease severity. This study was undertaken to investigate whether T cell–derived exosomal proteins play a role in SLE pathogenesis. Methods We characterized proteins in T cell–derived exosomes from SLE patients and healthy controls by MACSPlex exosome analysis and proteomics. To study the potential pathogenic functions of the exosomal protein identified, we generated and characterized T cell–specific transgenic mice that overexpressed that protein in T cells. Results We identified eosinophil cationic protein (ECP, also called human RNase III) as overexpressed in SLE T cell–derived exosomes. T cell–specific ECP–transgenic mice (n = 5 per group) displayed early induction of serum interferon‐γ (IFNγ) levels (P = 0.062) and inflammation of multiple tissue types. Older T cell–specific ECP–transgenic mice (n = 3 per group) also displayed an increase in follicular helper T cell and plasma B cell numbers, and in autoantibody levels (P < 0.01). Single‐cell RNA sequencing showed the induction of IFNγ messenger RNA (P = 2.2 × 10‐13) and inflammatory pathways in ECP‐transgenic mouse T cells. Notably, adoptively transferred ECP‐containing exosomes stimulated serum autoantibody levels (P < 0.01) and tissue IFNγ levels in the recipient mice (n = 3 per group). The transferred exosomes infiltrated into multiple tissues of the recipient mice, resulting in hepatitis, nephritis, and arthritis. Conclusion Our findings indicate that ECP overexpression in T cells or T cell–derived exosomes may be a biomarker and pathogenic factor for nephritis, hepatitis, and arthritis associated with SLE.