title: Phenotypic changes to the endogenous antigen-specific CD8+ T cell response correlates with the development and resolution of allergic airway disease.
abstract: The role of CD8(+) T cells in the pathogenesis of asthma remains controversial, as both pro- and anti-inflammatory functions have been suggested. This study was designed to examine the endogenous CD8(+) T cell response in a biphasic ovalbumin (OVA)-induced model of allergic airway disease (AAD) and its subsequent resolution with the development of local inhalational tolerance (LIT). We observed increases in OVA-specific CD8(+) T cell numbers in the local lung compartments (bronchoalveolar lavage, lung tissue, hilar lymph node) at AAD and LIT; systemic compartments (spleen, inguinal lymph node) displayed no such increases in CD8(+) T cell numbers. OVA-specific CD8(+) T cells appeared to exhibit plasticity both phenotypically and functionally. They possessed pro-inflammatory characteristics at AAD, with high phenotypic expression of CD11a and increased functional expression of granzyme B and interferon-γ. In contrast, at LIT they showed increased phenotypic expression of the inhibitory marker NKG2A and functionally did not produce granzyme B or interferon-γ. In addition, in a discontinuous model the OVA-specific CD8(+) T cells could be recalled on re-exposure to OVA, demonstrating memory. Finally, confocal microscopy results showed that OVA-specific CD8(+) T cells at AAD are associated with B cell aggregates in lung tissue. These B cell aggregates resembled tertiary ectopic lymphoid tissue and may thus provide a local environment for the salient cellular interactions that contribute to the development of LIT.
authors.affiliation: Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: McNamara
authors.forename: Craig M
authors.initials: CM
authors.lastname: Schramm
authors.forename: Anurag
authors.initials: A
authors.lastname: Singh
authors.forename: Eric R
authors.initials: ER
authors.lastname: Secor
authors.forename: Linda A
authors.initials: LA
authors.lastname: Guernsey
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrançois
authors.forename: Roger S
authors.initials: RS
authors.lastname: Thrall
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001980:Bronchi / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D007108:Immune Tolerance; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000032:analysis; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D055654:NK Cell Lectin-Like Receptor Subfamily C; D007371:Interferon-gamma; D010047:Ovalbumin; D053804:Granzymes; C509214:Gzmb protein, mouse