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T regulatory cells: aid or hindrance in the clearance of disease?

Coleman CA, Muller-Trutwin MC, Apetrei C, Pandrea I - J. Cell. Mol. Med. (2007 Nov-Dec)

Bottom Line: CD4+ CD25+ T regulatory cells (Tregs) are classified as a subset of T cells whose role is the suppression and regulation of immune responses to self and non-self.Since their discovery in the early 1970s, the role of CD4+ CD25+ Tregs in both autoimmune and infectious disease has continued to expand.In addition, advances made in the purification and manipulation of CD4+ CD25+ Tregs using new cell markers, techniques and antibodies are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA, USA.

ABSTRACT
CD4+ CD25+ T regulatory cells (Tregs) are classified as a subset of T cells whose role is the suppression and regulation of immune responses to self and non-self. Since their discovery in the early 1970s, the role of CD4+ CD25+ Tregs in both autoimmune and infectious disease has continued to expand. This review examines the recent advances on the role CD4+ CD25+ Tregs may be playing in various diseases regarding progression or protection. In addition, advances made in the purification and manipulation of CD4+ CD25+ Tregs using new cell markers, techniques and antibodies are discussed. Ultimately, an overall understanding of the exact mechanism which CD4+ CD25+ Tregs implement during disease progression will enhance our ability to manipulate CD4+ CD25+ Tregs in a clinically beneficial manner.

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Related in: MedlinePlus

Non-human primates display the two isoforms of FoxP3 as seen in human beings. PCR amplification of Rhesus macaques RNA with primers specific to the FoxP3 gene resulted in two bands that follow the same pattern of a full length FoxP3 (1293 bp) and a exon 2 FoxP3 (1191 bp) as seen in human beings. The same pattern was observed in amplified cDNA from African green monkeys. Promega's 1Kb ladder was used in this gel.
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fig04: Non-human primates display the two isoforms of FoxP3 as seen in human beings. PCR amplification of Rhesus macaques RNA with primers specific to the FoxP3 gene resulted in two bands that follow the same pattern of a full length FoxP3 (1293 bp) and a exon 2 FoxP3 (1191 bp) as seen in human beings. The same pattern was observed in amplified cDNA from African green monkeys. Promega's 1Kb ladder was used in this gel.

Mentions: As discussed above, FoxP3 is considered essential for CD4+ CD25+ Tregs to function properly. Recently, transduction of CD4+ CD25neg T cells with a FoxP3 expression vector has resulted in increased levels of CD4+ CD25+ Tregs. In human beings, two isoforms of the FoxP3 protein were identified by Western Blot and reverse-transcription (RT)-PCR analysis, in contrast to only one isoform found in mice [64, 155–157]. Our lab has also observed by RT-PCR two isoforms of the FoxP3 protein in non-human primates (NHPs) (Fig. 4). In human beings, one isoform closely resembles the mouse FoxP3 while the other isoform is apparently encoded by mRNA lacking exon 2 (Amino Acids 71–105). In addition, Smith et al. reported a third isoform of FoxP3 in human beings that is lacking both exon 2 and 7 [156]. The significance of the isoforms in human beings is not immediately apparent. Recent evidence using a retrovirus-based overexpression strategy showed that overexpression of either isoform resulted in similar phenotypes in transfected CD4+ T cells [155, 156]. Co-expression of FoxP3 and FoxP3 (Δexon2) isoforms in transfected CD4+ T cells resulted in elevated suppression of the cytokines IL-2 and IFN-γ and also increased expression of CD4+ CD25+ Tregs surface markers as compared to the expression of either individual isoform alone [155]. However, CD4+ T cells transfected with either FoxP3 or FoxP3 (exon2) isoforms did not have increased suppressive capabilities as compared to naturally occurring CD4+ CD25+ Tregs, suggesting that either isoform of FoxP3 is adequate for inducing the suppressive abilities of CD4+ CD25+ Tregs.


T regulatory cells: aid or hindrance in the clearance of disease?

Coleman CA, Muller-Trutwin MC, Apetrei C, Pandrea I - J. Cell. Mol. Med. (2007 Nov-Dec)

Non-human primates display the two isoforms of FoxP3 as seen in human beings. PCR amplification of Rhesus macaques RNA with primers specific to the FoxP3 gene resulted in two bands that follow the same pattern of a full length FoxP3 (1293 bp) and a exon 2 FoxP3 (1191 bp) as seen in human beings. The same pattern was observed in amplified cDNA from African green monkeys. Promega's 1Kb ladder was used in this gel.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401294&req=5

fig04: Non-human primates display the two isoforms of FoxP3 as seen in human beings. PCR amplification of Rhesus macaques RNA with primers specific to the FoxP3 gene resulted in two bands that follow the same pattern of a full length FoxP3 (1293 bp) and a exon 2 FoxP3 (1191 bp) as seen in human beings. The same pattern was observed in amplified cDNA from African green monkeys. Promega's 1Kb ladder was used in this gel.
Mentions: As discussed above, FoxP3 is considered essential for CD4+ CD25+ Tregs to function properly. Recently, transduction of CD4+ CD25neg T cells with a FoxP3 expression vector has resulted in increased levels of CD4+ CD25+ Tregs. In human beings, two isoforms of the FoxP3 protein were identified by Western Blot and reverse-transcription (RT)-PCR analysis, in contrast to only one isoform found in mice [64, 155–157]. Our lab has also observed by RT-PCR two isoforms of the FoxP3 protein in non-human primates (NHPs) (Fig. 4). In human beings, one isoform closely resembles the mouse FoxP3 while the other isoform is apparently encoded by mRNA lacking exon 2 (Amino Acids 71–105). In addition, Smith et al. reported a third isoform of FoxP3 in human beings that is lacking both exon 2 and 7 [156]. The significance of the isoforms in human beings is not immediately apparent. Recent evidence using a retrovirus-based overexpression strategy showed that overexpression of either isoform resulted in similar phenotypes in transfected CD4+ T cells [155, 156]. Co-expression of FoxP3 and FoxP3 (Δexon2) isoforms in transfected CD4+ T cells resulted in elevated suppression of the cytokines IL-2 and IFN-γ and also increased expression of CD4+ CD25+ Tregs surface markers as compared to the expression of either individual isoform alone [155]. However, CD4+ T cells transfected with either FoxP3 or FoxP3 (exon2) isoforms did not have increased suppressive capabilities as compared to naturally occurring CD4+ CD25+ Tregs, suggesting that either isoform of FoxP3 is adequate for inducing the suppressive abilities of CD4+ CD25+ Tregs.

Bottom Line: CD4+ CD25+ T regulatory cells (Tregs) are classified as a subset of T cells whose role is the suppression and regulation of immune responses to self and non-self.Since their discovery in the early 1970s, the role of CD4+ CD25+ Tregs in both autoimmune and infectious disease has continued to expand.In addition, advances made in the purification and manipulation of CD4+ CD25+ Tregs using new cell markers, techniques and antibodies are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA, USA.

ABSTRACT
CD4+ CD25+ T regulatory cells (Tregs) are classified as a subset of T cells whose role is the suppression and regulation of immune responses to self and non-self. Since their discovery in the early 1970s, the role of CD4+ CD25+ Tregs in both autoimmune and infectious disease has continued to expand. This review examines the recent advances on the role CD4+ CD25+ Tregs may be playing in various diseases regarding progression or protection. In addition, advances made in the purification and manipulation of CD4+ CD25+ Tregs using new cell markers, techniques and antibodies are discussed. Ultimately, an overall understanding of the exact mechanism which CD4+ CD25+ Tregs implement during disease progression will enhance our ability to manipulate CD4+ CD25+ Tregs in a clinically beneficial manner.

Show MeSH
Related in: MedlinePlus