Journal
JOURNAL OF IMMUNOLOGY
Volume 185, Issue 7, Pages 3809-3813Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1000971
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Funding
- National Institutes of Health [R01HL094601, KO8HL083983, KO8CA131097]
- American Association for Thoracic Surgery
- Melanoma Research Foundation
- Siteman Cancer Center American Cancer Society
- NATIONAL CANCER INSTITUTE [K08CA131097] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [K08HL083983, R01HL094601] Funding Source: NIH RePORTER
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The interaction of CD4(+) T cells with MHC class II (MHCII)-expressing hematopoietic APCs plays a critical role in both the generation of protective immune responses and maintenance of tolerance in the lung. The functional significance of MHCII expression by nonhematopoietic stromal cells, however, has not been defined in vivo. Using a novel mouse model of orthotopic left lung transplantation, we demonstrate that selective elimination of MHCII expression on nonhematopoietic cells leads to an inflammatory response as a result of reduced peripheral generation of regulatory CD4(+) T cells. Absence of MHCII expression on nonhematopoietic cells also inhibits local growth of metastatic pulmonary tumor. These findings indicate that nonhematopoietic cells play a previously unrecognized role in downregulating inflammatory responses in nonlymphoid tissues. The Journal of Immunology, 2010, 185: 3809-3813.
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