Measuring the diaspora for virus-specific CD8(+) T cells

The CD8(+) T cell diaspora has been analyzed after secondary challenge with an influenza A virus that replicates only in the respiratory tract. Number s of (DNP366)-N-b- and D(b)PA(224)-specific CD8+ T cells were measured by t etramer staining at the end of the recall response, then followed sequentia lly in the lung, lymph nodes, spleen, blood, and other organs. The extent o f clonal expansion did not reflect the sizes of the preexisting memory T ce ll pools. Although the high-frequency CD8(+) tetramer(+) populations in the pneumonic lung and mediastinal lymph nodes fell rapidly from peak values, the "whole mouse" virus-specific CD8(+) T cell counts decreased only 2-fold over the 4 weeks after infection, then subsided at a fairly steady rate to reach a plateau at about 2 months. The largest numbers were found througho ut in the spleen, then the bone marrow. The CD8(+)D(b)NP(366)(+) and CD8(+) D(b)PA(224)(+) sets remained significantly enlarged for at least 4 months, declining at equivalent rates while retaining the nucleoprotein > acid poly merase immunodominance hierarchy characteristic of the earlier antigen-driv en phase. Lowest levels of the CD69 "activation marker" were detected consi stently on virus-specific CD8(+) T cells in the blood, then the spleen. Tho se in the bone marrow and liver were intermediate, and CD69(hi) T cells wer e very prominent in the regional lymph nodes and the nasal-associated lymph oid tissue. Any population of "resting" CD8(+) memory T cells is thus pheno typically heterogeneous, widely dispersed, and subject to broad homeostatic and local environmental effects irrespective of epitope specificity or mag nitude.