Differential mRNA expression in circulating gammadelta T lymphocyte subsets defines unique tissue-specific functions.
To elucidate the functions of circulating gammadelta T cells, in the absence of antigen stimulation, the differential gene expression of two circulating gammadelta T cell subsets was analyzed. The two subsets, with distinct trafficking phenotypes in young calves, were GD3.5(+), CD8(-), WC1(+) or GD3.5(-), CD2(+), WC1(-), and 90-100% CD8(+) and were sorted based on GD3.5 and gammadelta T cell receptor expression. Results from two different human arrays probed with cDNA from these gammadelta T cell subsets indicated that they have markedly different tissue-specific functions. The genes preferentially expressed by GD3.5(+) (CD8(-)) gammadelta T cells demonstrated that they were highly activated, proliferative, and inflammatory, whereas those expressed by GD3.5(-) (primarily CD8(+)) gammadelta T cells were involved in promoting quiescence, consistent with a role for gammadelta T cells as sentinel mucosal cells, and several were interferon-regulated genes. Gene expression and phenotypic assays indicated that CD8(+) gammadelta T cells were apoptotic, whereas CD8(-) gammadelta T cells were apoptosis-resistant. Differential expression of multiple genes was confirmed in both arrays: That of 14 genes was confirmed by quantitative reverse transcriptase-polymerase chain reaction and that of seven proteins was confirmed by flow cytometry. This novel, genomic analysis of circulating gammadelta T cell subsets, without confounding effects of the tissue microenvironment, offers new insight into the biology and development of neonatal gammadelta T cells.
Hedges
Jodi F
JF
Department of Veterinary Molecular Biology, Marsh Laboratory, Montana State University, 19th and Lincoln, Bozeman, MT 59717, USA.
Cockrell
Diane
D
Jackiw
Larissa
L
Meissner
Nicole
N
Jutila
Mark A
MA
D000818:Animals; D002417:Cattle; D020869:Gene Expression Profiling; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D016692:Receptors, Antigen, T-Cell, gamma-delta