Immune reconstitution disease is associated with the prior absence of host M avium–specific T-cell responses, rather than lymphopenia-driven T-cell expansion. (A) Uninfected WT, TCRα^−/−, and OT-II recipients received CFSE-labeled Thy1.1⁺ P25 CD4 T cells (2 × 10⁶/mouse), and lymph nodes were harvested on day 7 after transfer and analyzed for CFSE dilution. Histograms are gated on CD4⁺Thy1.1⁺ donor P25 CD4 T cells. (B) M avium–infected WT, TCRα^−/−, or OT-II mice were injected with P25 CD4 T cells (2 × 10⁶), and survival was monitored. (C) CD4 T cells (2 × 10⁶) isolated from C57Bl/6 mice were transferred into M avium–infected TCRα^−/−, OT-II, or P25 recipient mice and weight loss was monitored. The shaded area between the traveling error bars represents the SD. (D) Survival of mice depicted in panel C, n = 5/group. All of the data shown were representative of 2 independent experiments performed.