Abstract
The CD8
+
T cell diaspora has been analyzed after
secondary challenge with an influenza A virus that replicates only in
the respiratory tract. Numbers of D
b
NP
366
- and
D
b
PA
224
-specific CD8
+
T cells were
measured by tetramer staining at the end of the recall response, then
followed sequentially in the lung, lymph nodes, spleen, blood, and
other organs. The extent of clonal expansion did not reflect the sizes
of the preexisting memory T cell 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 throughout 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 polymerase
immunodominance hierarchy characteristic of the earlier antigen-driven
phase. Lowest levels of the CD69 “activation marker” were
detected consistently on virus-specific CD8
+
T cells in the
blood, then the spleen. Those in the bone marrow and liver were
intermediate, and CD69
hi
T cells were very prominent in the
regional lymph nodes and the nasal-associated lymphoid tissue. Any
population of “resting” CD8
+
memory T cells is thus
phenotypically heterogeneous, widely dispersed, and subject to broad
homeostatic and local environmental effects irrespective of epitope
specificity or magnitude.
