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Published online July 22, 2009
The Journal of Immunology, 2009, 183, 2622 -2631
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0802180

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NK Cells Interfere with the Generation of Resistance against Mycoplasma Respiratory Infection following Nasal-Pulmonary Immunization1

Sheetal Bodhankar*, Mathew D. Woolard{dagger}, Xiangle Sun* and Jerry W. Simecka2,*

* Department of Molecular Biology and Immunology, University of North Texas Health Science Center, Fort Worth, TX 76107; and {dagger} Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130

The purpose of the present study was to determine the impact of NK cells on the development of protective adaptive immunity in response to nasal-pulmonary immunization against mycoplasma. Depletion of NK cells before nasal-pulmonary immunization enhanced resistance to mycoplasma respiratory infection. The effect of NK cells on the generation of protective immunity in lungs was dependent on lymphoid cells, as immunization of either SCID mice or immunocompetent mice depleted of CD4+ T cells did not demonstrate any increased resistance in the presence or absence of NK cells. The presence of NK cells at the time of nasal-pulmonary immunization modulated mycoplasma-specific cytokine responses in lungs and lower respiratory nodes. In particular, NK cells skewed the mycoplasma-specific T cell cytokine responses in the draining lymph nodes to higher IL-4, IL-13, and IL-17 while lowering IFN-{gamma} responses. Adoptive transfer of total lung lymphocytes isolated from immunized mice into naive mice led to a significant reduction in the mycoplasma numbers in lungs, and the resistance was greater if cells were obtained from immunized mice that were depleted of NK cells. Similar results were obtained if purified B cells, T cells, or CD4+ T cells were used. Interestingly, this is the first time that a favorable role of functional CD4+ T cells in mediating protection in mycoplasma respiratory disease was demonstrated. Thus, NK cells can influence the responses of multiple lymphocyte populations capable of mediating resistance to mycoplasma infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Public Health Service Grant R01AI042075 (to J.W.S.). The Flow Cytometry Facility was supported by a shared instrument grant from the National Institutes of Health.

2 Address correspondence and reprint requests to Dr. Jerry W. Simecka, Department of Molecular Biology and Immunology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107. E-mail address: jsimecka{at}hsc.unt.edu

3 Abbreviations used in this paper: LRN, lower respiratory lymph node; anti-asialo GM1, anti-asialo ganglio-N-tetraosylceramide.







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