CD8+ T cell contributions to allergen induced pulmonary inflammation and airway hyperreactivity.
The pathogenesis of asthma has been linked to the production of type 2 cytokines, which can be expressed by several cell types in the lung. These studies investigated CD8(+) T cell responses in a murine cockroach antigen (CRA) model of asthma. The results from these present studies show that depletion of CD8(+) T cells after allergen sensitization to CRA significantly reduces airway hyperreactivity, airway eosinophilia and pulmonary type 2 cytokine levels. The data demonstrate that CD8(+) T cells from CRA-sensitized mice can produce type 2 cytokines IL-4, IL-5 and IL-13 upon antigen challenge, and that the transfer of these cells into naive mice will cause airway hyperreactivity when exposed to CRA. We found that the transferred airway response is dependent on both IL-4 and IL-13 from CD8(+) T cells using cytokine knockout mice. Compared to CD4(+) T cells, CD8(+) T cells were not as numerous in the lungs of sensitized and challenged mice, but were as efficacious in the transfer of airway disease. The most severe airway response was observed when both CD4(+) and CD8(+) T cells were transferred at the same time. Altogether, these studies highlight a role for CD8(+) T lymphocytes in the development of allergen-induced airway responses.
Schaller
Matthew A
MA
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Lundy
Steven K
SK
Huffnagle
Gary B
GB
Lukacs
Nicholas W
NW
D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002478:Cells, Cultured; D003058:Cockroaches / Q000276:immunology; D016207:Cytokines / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D016207:Cytokines