Vγ1+ γδ T cells reduce IL-10-producing CD4+CD25+ T cells in the lung of ovalbumin-sensitized and challenged mice.
In OVA-sensitized and challenged mice, gammadelta T cells expressing Vgamma1 enhance airway hyperresponsiveness (AHR) but the underlying mechanism is unclear. These cells also reduce IL-10 levels in the airways, suggesting that they might function by inhibiting CD4(+)CD25(+) regulatory T cells (T(reg)) or other CD4(+) T cells capable of producing IL-10 and suppressing AHR. Indeed, sensitization and challenge with OVA combined with inactivation of Vgamma1(+) cells increased CD4(+)CD25(+) cells in the lung, and markedly those capable of producing IL-10. The cellular change was associated with increased IL-10 and TGF-beta levels in the airways, and a decrease of IL-13. T(reg) include naturally occurring Foxp3(+) T(reg), inducible Foxp3(-) T(reg), and antigen-specific T(reg) many of which express folate receptor 4 (FR4). Although Foxp3 gene expression in the lung was also increased pulmonary CD4(+) T cells, expressing Foxp3-protein or FR4 remained stable. Therefore, the inhibition by Vgamma1(+) gammadelta T cells might not be targeting Foxp3(+) T(reg) but rather CD4(+) T cells destined to produce IL-10.
Hahn
Youn-Soo
YS
Department of Pediatrics, College of Medicine and Medical Research Institute, Chungbuk National University, 62 Kaeshin-dong, Hungduk-gu, Cheongju 361-711, Republic of Korea. yshahn@chungbuk.ac.kr
Ji
Xu Yin
XY
Woo
Sung-Il
SI
Choi
Young-Ki
YK
Song
Min-Seok
MS
Shin
Kyung-Seop
KS
Jin
Niyun
N
O'Brien
Rebecca L
RL
Born
Willi K
WK
D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000276:immunology; D015704:CD4 Antigens / Q000096:biosynthesis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D019675:Genes, T-Cell Receptor gamma / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D019138:Antibodies, Blocking; D015704:CD4 Antigens; D002352:Carrier Proteins; C418974:FOXP3 protein, human; D058973:Folate Receptors, GPI-Anchored; D051858:Forkhead Transcription Factors; D018793:Interleukin-13; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; C543634:folate receptor 4, mouse; D016753:Interleukin-10; D000536:Aluminum Hydroxide; D010047:Ovalbumin