CD43 signals induce Type One lineage commitment of human CD4+ T cells

Ramírez-Pliego, Oscar; Escobar-Zárate, Diana L; Rivera-Martínez, Gemma M; Cervantes-Badillo, Mayte Guadalupe; Esquivel-Guadarrama, Fernando; Rosas-Salgado, Gabriela; Rosenstein, Yvonne; Santana, María Angélica

doi:10.1186/1471-2172-8-30

Cited by 16 publications

(21 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Phosphorylation of CD43 cytoplasmic tail leads to its association with ezrin-radixin-moesin (ERM) cytoskeletal proteins and full T cell activation while inhibition of CD43 interaction with ERM proteins results in decreased cytokine production (6–8). These findings are in agreement with reports showing that signaling through CD43 increases T-bet expression and inhibits GATA-3 gene transcription, predisposing T cells toward a Th1 lineage commitment and inducing IFN-γ expression (9–11). Conversely, CD43-deficient T cells preferentially differentiate into Th2 cells that produce high levels of IL-4, IL-5, and IL-13 (12).…”

Section: Introductionsupporting

confidence: 93%

See 1 more Smart Citation

CD43-Mediated IFN-γ Production by CD8+ T Cells Promotes Abdominal Aortic Aneurysm in Mice

Zhou

Yan

Cannon

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

CD43 is a glycosylated surface protein abundantly expressed on lymphocytes. Its role in immune responses has been difficult to clearly establish, with evidence supporting both costimulatory and inhibitory functions. In addition, its contribution to disease pathogenesis remains elusive. Using a well-characterized murine model of elastase-induced abdominal aortic aneurysm (AAA) that recapitulates many key features of the human disease we established that the presence of CD43 on T cells is required for AAA formation. Moreover, we found that IFN-γ producing CD8+ T cells, but not CD4+ T cells, promote the development of aneurysm by enhancing cellular apoptosis and matrix metalloprotease activity. Reconstitution with IFN-γ producing CD8+ T cells or recombinant IFN-γ promotes the aneurysm phenotype in CD43−/− mice while IFN-γ antagonism abrogates disease in WT animals. Furthermore we showed that the presence of CD43 with an intact cytoplasmic domain capable of binding to ezrin-radixin-moesin cytoskeletal proteins is essential for optimal in vivo IFN-γ production by T cells and aneurysm formation. We have thus identified a robust physiologic role for CD43 in a relevant animal model and established an important in vivo function for CD43-dependent regulation of IFN-γ production. These results further suggest that IFN-γ antagonism or selective blockade of CD43+CD8+ T cell activities merits further investigation for immunotherapy in AAA.

show abstract

Section: Introductionsupporting

confidence: 93%

“…Although CD43 has been linked to many T cell activities (3, 9–11, 30, 39–41), its physiologic contribution to T cell functions in inflammation and diseases remains a point of debate. Previous studies have shown that the absence of CD43 results in a preferential Th2 differentiation and the exacerbation of Th2-mediated diseases (12).…”

Section: Discussionmentioning

confidence: 99%

CD43-Mediated IFN-γ Production by CD8+ T Cells Promotes Abdominal Aortic Aneurysm in Mice

Zhou

Yan

Cannon

et al. 2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…It remains to be determined how the presence or absence of CD43 on T cells is regulating Th cell differentiation. Studies in human T cells have shown that CD43 costimulation in the presence and absence of TCR stimulation can induce IFN-␥ production and promote Th1 differentiation (42)(43)(44)(45). However, these findings have not been replicated in murine systems, making it unclear whether this plays a role in our model.…”

Section: -Immunized Cd43mentioning

confidence: 92%

CD43 Regulates Th2 Differentiation and Inflammation

Cannon

Collins

Mody

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

CD43 is a highly glycosylated transmembrane protein that regulates T cell activation. CD43−/− T cells are hyperproliferative and the cytoplasmic tail of CD43 has been found to be sufficient to reconstitute wild-type proliferation levels, suggesting an intracellular mechanism. In this study, we report that upon TCR ligation CD43−/− T cells demonstrated no increase in tyrosine phosphorylation but a decreased calcium flux. Interestingly, CD43−/− T cells preferentially differentiated into Th2 cells in vitro, and CD43−/− T cells show increased GATA-3 translocation into the nucleus. In vivo, CD43−/− mice exhibited increased inflammation in two separate models of Th2-mediated allergic airway disease. In contrast, in Th1-mediated diabetes, nonobese diabetic CD43−/− mice did not significantly differ from wild-type mice in disease onset or progression. Th1-induced experimental autoimmune encephalomyelitis to MOG35–55 was also normal in the CD43−/− mice. Nonetheless, the CD43−/− mice produced more IL-5 when restimulated with MOG35–55 in vitro and demonstrated decreased delayed-type hypersensitivity responses. Together, these data demonstrate that although CD43−/− T cells preferentially differentiate into Th2 cells, this response is not sufficient to protect against Th1-mediated autoimmune responses.

show abstract

“…ϩ T cells into a TH1 pattern (65). CD127 (IL-7 receptor) is another marker that has also been used by numerous groups to distinguish CD8 ϩ and CD4 ϩ memory T cells in HIV-1 patients (18,54,67,85).…”

mentioning

confidence: 99%