Expression of functional CD8α β heterodimer on rat γ δ T cells does not correlate with the CDR3 length of the TCRδ chain predicted for MHC class I-restricted antigen recognition
Abstract:In accordance with their lack of MHC restriction, most mouse and human γ δ T cells express neither the CD4 nor CD8(α β) coreceptor. In striking contrast, up to 80% of splenic rat γ δ T cells express the CD8α β isoform of CD8, which for the α β T cell subset serves as a marker for MHC class I‐restricted cells. We compared CD8 on α β and γ δ T cells with regard to co‐stimulatory function and correlation of CD8 expression with TCRDV usage and CDR3δ length. In both subsets, CD8 acted as a co‐stimulatory molecule i… Show more
“…In our study, we observed that a portion of ␥␦ T cells expressed CD8␣ as previously described in rats (34). The CD8 appeared to be functional and not restricted to oligoclonal ␥␦ T cells.…”
Conclusions: The simple observation of a CD3 bright T-cell subset on CD3/CD4/CD8 routine analysis suggests a high ␥␦ T-cell fraction and, in our opinion, should be followed by a complementary analysis to determine precisely the number of ␥␦ T cells and to identify their CD8␣/ phenotype. When CD3 bright T cells/l were more than 40%, high ␥␦ T cells were detected in more than 87% of cases, with a specificity of 76%. Occasionally, the CD3 bright subset appeared to be strongly homogeneous, suggesting an oligoclonal proliferation that could possibly reveal a chronic localized stimulation or an early lymphoproliferative disorder. Because the ␥␦ T cells have interesting immunological peculiarities, the clinical significance of their quantitative abnormality should be clarified in diseases such as HIV, organ transplantation, autoimmunity and lymphoma.
“…In our study, we observed that a portion of ␥␦ T cells expressed CD8␣ as previously described in rats (34). The CD8 appeared to be functional and not restricted to oligoclonal ␥␦ T cells.…”
Conclusions: The simple observation of a CD3 bright T-cell subset on CD3/CD4/CD8 routine analysis suggests a high ␥␦ T-cell fraction and, in our opinion, should be followed by a complementary analysis to determine precisely the number of ␥␦ T cells and to identify their CD8␣/ phenotype. When CD3 bright T cells/l were more than 40%, high ␥␦ T cells were detected in more than 87% of cases, with a specificity of 76%. Occasionally, the CD3 bright subset appeared to be strongly homogeneous, suggesting an oligoclonal proliferation that could possibly reveal a chronic localized stimulation or an early lymphoproliferative disorder. Because the ␥␦ T cells have interesting immunological peculiarities, the clinical significance of their quantitative abnormality should be clarified in diseases such as HIV, organ transplantation, autoimmunity and lymphoma.
“…cyte kinase (Lck) association of the CD8αβ heterodimers of γδ T-cells was indistinguishable from that of CD8αβ-expressing αβ T-cells.Nevertheless, analysis of CDR3δ lengths of TCRs expressed by the different T-cell types (CD8αβ-positive vs. CD8-negative) showed no difference in length and the average length was even higher than for homologous mouse TCR-δ chains, indicating that these TCRs cannot act in an αβ TCR-like MHC-restricted manner 70. Morerelated to classical MHC-restricted αβ T-cells are recently discovered γδ T-cells with specificity for melanoma antigen recognized by T-cells 1 (MART-1) peptides presented by HLA-A*0201.…”
The discovery that butyrophilins (BTNs) control the development and activity of human and mouse γδ T-cell subsets, 1-3 the increasing knowledge on γδ T-cell antigen receptor (TCR)-ligand interaction 4,5 together with the exploding interest in cell-based therapeutics stimulated a general interest in γδ T-cells during the last years. 6 One fascinating aspect of γδ T-cells is their Janus-faced nature. Cells with γδ TCRs are found in all classes of jawed vertebrates, yet they can be highly divergent between species and specialized within an organism. There are clear indications for functions in the adaptive immune response, yet they also show features of an innate immune cell. 7
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