The Journal of Experimental Medicine
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Published online 30 September 2002 doi:10.1084/jem.20021052
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© Rockefeller University Press, 0022-1007/2002/10/957/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 7, October 7, 2002 957-968

CD4 Effector T Cell Subsets in the Response to Influenza : Heterogeneity, Migration, and Function



Eulogia Román1, Ellen Miller1, Allen Harmsen2, James Wiley2, Ulrich H. von Andrian3, Gail Huston1 and Susan L. Swain1

1 Trudeau Institute, Saranac Lake, NY 12983
2 Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717
3 Department of Pathology, Harvard Medical School, Boston, MA 02115

Address correspondence to Dr. Susan L. Swain, Trudeau Institute, 100 Algonquin Ave., Saranac Lake, NY 12983. Phone: 518-891-3080; Fax: 518-891-5126; E-mail: sswain{at}northnet.org

The immune response of naive CD4 T cells to influenza virus is initiated in the draining lymph nodes and spleen, and only after effectors are generated do antigen-specific cells migrate to the lung which is the site of infection. The effector cells generated in secondary organs appear as multiple subsets which are a heterogeneous continuum of cells in terms of number of cell divisions, phenotype and function. The effector cells that migrate to the lung constitute the more differentiated of the total responding population, characterized by many cell divisions, loss of CD62L, down-regulation of CCR7, stable expression of CD44 and CD49d, and transient expression of CCR5 and CD25. These cells also secrete high levels of interferon {gamma} and reduced levels of interleukin 2 relative to those in the secondary lymphoid organs. The response declines rapidly in parallel with viral clearance, but a spectrum of resting cell subsets reflecting the pattern at the peak of response is retained, suggesting that heterogeneous effector populations may give rise to corresponding memory populations. These results reveal a complex response, not an all-or-none one, which results in multiple effector phenotypes and implies that effector cells and the memory cells derived from them can display a broad spectrum of functional potentials.

Key Words: memory • inflammation • migration • chemokine receptors • cytokines


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