A murine locus on chromosome 18 controls NKT cell homeostasis and Th cell differentiation.

Zhang F, Liang Z, Matsuki N, Van Kaer L, Joyce S, Wakeland EK, Aune TM
J Immunol. 2003 171 (9): 4613-20

PMID: 14568935 · DOI:10.4049/jimmunol.171.9.4613

Th cell differentiation is a critical event in the adaptive immune response. C57BL strains develop predominant Th1 responses while BALB/c develops a predominant Th2 response. To identify quantitative trait loci controlling this variation, we performed Th1/Th2 differentiation assays of F(1) x BALB/c progeny. A single strong quantitative trait locus was identified on chromosome 18, with weaker effects detectable on chromosomes 5, 12, and 14. By preparing a congenic BALB.B10.D2c18 strain, we were able to demonstrate that this single locus was sufficient to "repolarize" spleen cell cultures. This difference was not due to intrinsic differences in CD4(+) T cells. Rather, introgression of the chromosome 18 locus into BALB/c disrupted Va14Ja18 NKT cell homeostasis resulting in the almost complete absence of this T cell subset. Taken together, these data indicate that genes within chromosome 18 control strain-dependent development of Va14Ja18 NKT cells.

MeSH Terms (26)

Animals Antigens, CD1 Antigens, CD1d Cell Differentiation Cells, Cultured Chromosome Mapping Crosses, Genetic Genetic Carrier Screening Genetic Linkage Homeostasis Immunophenotyping Interleukin-4 Killer Cells, Natural Lymphocyte Depletion Mice Mice, Congenic Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Quantitative Trait Loci Spleen T-Lymphocytes, Helper-Inducer T-Lymphocyte Subsets Th1 Cells Th2 Cells

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