Protection from Respiratory Virus Infections Can Be Mediated by Antigen-specific CD4+ T Cells That Persist in the Lungs

doi:10.1084/jem.193.8.981

Published online 16 April 2001.

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© The Rockefeller University Press, 0022-1007/2001/4/981/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 8, April 16, 2001 981-986

Brief Definitive Report

Protection from Respiratory Virus Infections Can Be Mediated by Antigen-specific CD4⁺ T Cells That Persist in the Lungs

Robert J. Hogan^a, Weimin Zhong^a, Edward J. Usherwood^a, Tres Cookenham^a, Alan D. Roberts^a, and David L. Woodland^a
^a Trudeau Institute, Saranac Lake, New York 12983

Correspondence to: David L. Woodland, Trudeau Institute, P.O. Box 59, Saranac Lake, NY 12983. Tel:518-891-3080 Fax:518-891-5126 E-mail:dwoodland{at}trudeauinstitute.org.

Although CD4⁺ T cells have been shown to mediate protectivecellular immunity against respiratory virus infections, theunderlying mechanisms are poorly understood. For example, althoughphenotypically distinct populations of memory CD4⁺ T cells havebeen identified in different secondary lymphoid tissues, itis not known which subpopulations mediate protective cellularimmunity. In this report, we demonstrate that virus-specificCD4⁺ T cells persist in the lung tissues and airways for severalmonths after Sendai virus infection of C57BL/6 mice. A largeproportion of these cells possess a highly activated phenotype(CD44^hi, CD62L^lo, CD43^hi, and CD25^hi) and express immediateeffector function as indicated by the production of interferon ${gamma}$ after a 5-h restimulation in vitro. Furthermore, intratrachealadoptive transfer of lung memory cells into ß₂m-deficientmice demonstrated that lung-resident virus-specific CD4⁺ T cellsmediated a substantial degree of protection against secondaryvirus infection. Taken together, these data demonstrate thatactivated memory CD4⁺ T cells persisting at mucosal sites playa critical role in mediating protective cellular immunity.

Key Words: immunologic memory, immunity, mucosal, paramyxovirus, CD4⁺ Tlymphocytes

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