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Infection and Immunity, August 2001, p. 4790-4798, Vol. 69, No. 8
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.8.4790-4798.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Situ Activation of Helper T Cells in the Lung

Bindu Raju,¹ Chung F. Tung,^2, Debbie Cheng,³ Nora Yousefzadeh,² Rany Condos,¹ William N. Rom,¹ and Doris B. Tse^2,*

Division of Pulmonary and Critical Care Medicine¹ and Division of Infectious Disease and Immunology,² Department of Medicine, and Department of Environmental Medicine,³ New York University School of Medicine, New York, New York 10016

Received 12 December 2000/Returned for modification 15 February 2001/Accepted 10 May 2001

To better understand the lung and systemic responses of helper T cells mediating memory immunity to Mycobacterium tuberculosis, we used three- and four-color flow cytometry to study the surface phenotype of CD4⁺ lymphocytes. Bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) samples were obtained from a total of 25 subjects, including 10 tuberculosis (TB)-infected subjects, 8 purified-protein-derivative-negative subjects, and 7 purified-protein-derivative-positive subjects. In marked contrast to CD4⁺ lymphocytes from PB (9% ± 5% expressing CD45RA and CD29), the majority (55% ± 16%) of CD4⁺ lymphocytes in BAL (ALs) simultaneously expressed CD45RA, a naïve T-cell marker, and CD29, members of the very late activation family. Further evaluation revealed that CD4⁺ ALs expressed both CD45RA and CD45RO, a memory T-cell marker. In addition, the proportion of CD4⁺ lymphocytes expressing CD69, an early activation marker, was drastically increased in BAL fluid (83% ± 9%) compared to PB (1% ± 1%), whereas no significant difference was seen in the expression of CD25, the low-affinity interleukin 2 receptor (34% ± 15% versus 40% ± 16%). More importantly, we identified a minor population of CD69^bright CD25^bright CD4⁺ lymphocytes in BAL (10% ± 6%) that were consistently absent from PB (1% ± 1%). Thus, CD4⁺ lymphocytes in the lung paradoxically coexpress surface molecules characteristic of naïve and memory helper T cells as well as surface molecules commonly associated with early and late stages of activation. No difference was observed for ALs obtained from TB-infected and uninfected lung segments in this regard. It remains to be determined if these surface molecules are induced by the alveolar environment or if CD4⁺ lymphocytes coexpressing this unusual combination of surface molecules are selectively recruited from the circulation. Our data suggest that ex vivo experiments on helper T-cell subsets that display distinctive phenotypes may be pivotal to studies on the human immune response to potential TB vaccines.

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^* Corresponding author. Mailing address: OB-C&D Rm 646, Bellevue Hospital, 462 First Ave., New York, NY 10016. Phone: (212) 263-8848. Fax: (212) 263-0584. E-mail: tsed01{at}med.nyu.edu.

Present address: State University of New York, Downstate Medical Center, Brooklyn, NY 11203-2098.

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Infection and Immunity, August 2001, p. 4790-4798, Vol. 69, No. 8
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.8.4790-4798.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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