MHC class I-dependent Vγ4<sup>+</sup>pulmonary T cells regulate αβ T cell-independent airway responsiveness

Lahn, Michael; Kanehiro, Arihiko; Takeda, Katsuyuki; Terry, Jennifer; Hahn, Youn Soo; Aydintug, M. Kemal; Konowal, Anatole; Ikuta, Koichi; O’Brien, Rebecca L.; Gelfand, Erwin W.; Born, Willi K.

doi:10.1073/pnas.132519299

Cited by 70 publications

(132 citation statements)

References 34 publications

(35 reference statements)

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“…Our studies provide direct evidence that ␣␤ T cells, in addition to ␥␦ T cells, regulate ␥␦ T cell homeostasis. This finding is consistent with earlier observations that ␥␦ T cell number is increased in C57BL͞6 TCR␤ Ϫ/Ϫ mice, compared with wild-type C57BL͞6 mice (37,43) and may also explain why mice expressing a mutant form of linker for activation of T cells (LAT) (LAT Y7/8/9F ) develop a ␥␦ T cell lymphoproliferative disorder (44). Although the authors suggest that LAT plays a negative regulatory role in ␥␦ T cell homeostasis, the ␣␤ T cell population is dramatically reduced in LAT Y7/8/9F mice.…”

Section: Discussionsupporting

confidence: 93%

γδ T cell homeostasis is established in competition with αβ T cells and NK cells

French

Roark²,

Born³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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γδ T cells are a diverse population of lymphocytes that play an important role in immune regulation. The size of the γδ T cell pool is tightly regulated, comprising only 1-10% of total lymphoid T cells in mice and humans. We examined the homeostatic regulation of γδ T cells using a model of lymphopenia-induced homeostatic expansion. We found that IL-15 and, to a lesser extent, IL-7 play an important role in lymphoid γδ T cell homeostasis. Moreover, γδ T cell homeostatic expansion was limited not only by γδ T cells themselves but also by natural killer cells and αβ T cells. Our results suggest that CD8 + αβ T cells are the most potent inhibitors of γδ T cell homeostasis and exert their effect by competing for IL-15.

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Section: Discussionsupporting

confidence: 93%

γδ T cell homeostasis is established in competition with αβ T cells and NK cells

French

Roark²,

Born³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Differences in V␥1 (and V␦6) CDR3 sequences expressed at the early and late stages of the immune response to Lm implies the existence of unique V1␥ ϩ T cell clones at both time points that could confer and account for the different functional characteristics of early-and late-responding V␥1 ϩ T cells. This functional plasticity among pathogen-elicited V␥1/V␦6 T cells does not fit well, however, with the idea that ␥␦ T cell function is determined or dictated by TCRV␥ usage (27,28). Indeed, although this may be more applicable to the restricted and invariant epithelia-associated populations of ␥␦ T cells, the data presented in this study argue for the functional heterogeneity of systemic V␥1 ϩ T cell responses to infection are most likely influenced by their microenvironment and conditions of activation and, therefore, by the stage of infection.…”

Section: Discussionmentioning

confidence: 84%

“…The differential expression of TCR variable (V) genes has been widely used to distinguish between different populations (reviewed in Ref. 26) and has been used to assign specific functions to different subsets of ␥␦ T cells (27,28). The immune response to certain viral (13,17) and bacterial (29,30) infections is dominated by a single subset of ␥␦ T cells expressing TCRs encoded by the GV5S1 (V␥1; TCR-V␥ nomenclature used is that of Heilig and Tonegawa (31)) and TRADV15 (V␦6) gene families (32) that accumulate in sites of infection coincident with or after pathogen clearance.…”

mentioning

confidence: 99%

Delineation of the Function of a Major γδ T Cell Subset during Infection

Andrew

Newton

Dalton

et al. 2005

The Journal of Immunology

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γδ T cells play important but poorly defined roles in pathogen-induced immune responses and in preventing chronic inflammation and pathology. A major obstacle to defining their function is establishing the degree of functional redundancy and heterogeneity among γδ T cells. Using mice deficient in Vγ1+ T cells which are a major component of the γδ T cell response to microbial infection, a specific immunoregulatory role for Vγ1+ T cells in macrophage and γδ T cell homeostasis during infection has been established. By contrast, Vγ1+ T cells play no significant role in pathogen containment or eradication and cannot protect mice from immune-mediated pathology. Pathogen-elicited Vγ1+ T cells also display different functional characteristics at different stages of the host response to infection that involves unique and different populations of Vγ1+ T cells. These findings, therefore, identify distinct and nonoverlapping roles for γδ T cell subsets in infection and establish the complexity and adaptability of a single population of γδ T cells in the host response to infection that is not predetermined, but is, instead, shaped by environmental factors.

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“…Lung digestions were performed as described [18]. Briefly, minced lungs were exposed to a 20 ml enzymatic mixture containing 6 units of Dispase II (Roche Diagnostics, Indianapolis, Indiana, US), 2 μg of Collagenase II and 2 μg of Collagenase IV (Sigma, St. Louis, MO, US) at 37°C for 75 min.…”

Section: Pulmonary Cd4+ T Cell Isolationmentioning

confidence: 99%

IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection

Martin

Rino

et al. 2007

Microbes and Infection

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185

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IL-23 induces IL-17 production in activated CD4+ T cells and participates in host defense against many encapsulated bacteria. However, whether IL-23/IL-17 axis contributes to a Mycoplasma pneumoniae (Mp)-induced lung inflammation (e.g., neutrophils) has not been addressed. Using an acute respiratory Mp infection murine model, we found significantly up-regulated lung IL-23p19 mRNA in the early phase of infection (4 h), and alveolar macrophages were an important cell source of Mp-induced IL-23. We further showed that Mp significantly increased IL-17 protein levels in bronchoalveolar lavage (BAL). Lung gene expression of IL-17, IL-17C and IL-17F was also markedly up-regulated by Mp in vivo. IL-17 and IL-17F were found to be derived mainly from lung CD4+ T cells, and were increased upon IL-23 stimulation in vitro. In vivo blocking of IL-23p19 alone or in combination with IL-23/IL-12p40 resulted in a significant reduction of Mp-induced IL-17 protein and IL-17/IL-17F mRNA expression, which was accompanied by a trend toward reduced lung neutrophil recruitment, BAL neutrophil activity, and Mp clearance. However, IL-23 neutralization had no effect on Mp-induced lung IL-17C mRNA expression. These results demonstrate that IL-17/IL-17F production is IL-23-dependent in an acute Mp infection, and contributes to neutrophil recruitment and activity in lung defense against the infection.

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MHC class I-dependent Vγ4⁺pulmonary T cells regulate αβ T cell-independent airway responsiveness

Cited by 70 publications

References 34 publications

γδ T cell homeostasis is established in competition with αβ T cells and NK cells

γδ T cell homeostasis is established in competition with αβ T cells and NK cells

Delineation of the Function of a Major γδ T Cell Subset during Infection

IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection

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MHC class I-dependent Vγ4+pulmonary T cells regulate αβ T cell-independent airway responsiveness

Cited by 70 publications

References 34 publications

γδ T cell homeostasis is established in competition with αβ T cells and NK cells

γδ T cell homeostasis is established in competition with αβ T cells and NK cells

Delineation of the Function of a Major γδ T Cell Subset during Infection

IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection

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MHC class I-dependent Vγ4⁺pulmonary T cells regulate αβ T cell-independent airway responsiveness