+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Tpm1, a locus controlling IL-12 responsiveness, acts by a cell-autonomous mechanism

Tpm1, a locus controlling IL-12 responsiveness, acts by a cell-autonomous mechanism

Journal of Immunology 162(3): 1339-1347

Th phenotype development is controlled not only by cytokines but also by other parameters including genetic background. One site of genetic variation between murine strains that has direct impact on Th development is the expression of the IL-12 receptor. T cells from B10.D2 and BALB/c mice show distinct control of IL-12 receptor expression. When activated by Ag, B10.D2 T cells express functional IL-12 receptors and maintain IL-12 responsiveness. In contrast, under the same conditions, BALB/c T cells fail to express IL-12 receptors and become unresponsive to IL-12, precluding any Th1-inducing effects if subsequently exposed to IL-12. Previously, we identified a locus, which we termed T cell phenotype modifier 1 (Tpm1), on murine chromosome 11 that controls this differential maintenance of IL-12 responsiveness. In this study, we have produced a higher resolution map around Tpm1. We produced and analyzed a series of recombinants from a first-generation backcross that significantly narrows the genetic boundaries of Tpm1. This allowed us to exclude from consideration certain previous candidates for Tpm1, including IFN-regulatory factor-1. Also, cellular analysis of F1(B10.D2 x BALB/c) T cells demonstrates that Tpm1 exerts its effect on IL-12 receptor expression in a cell-autonomous manner, rather than through influencing the extracellular milieu. This result strongly implies that despite the proximity of our locus to the IL-13/IL-4 gene cluster, these cytokines are not candidates for Tpm1.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 018188211

Download citation: RISBibTeXText

PMID: 9973388

Related references

The non-protein coding breast cancer susceptibility locus Mcs5a acts in a non-mammary cell-autonomous fashion through the immune system and modulates T-cell homeostasis and functions. Breast Cancer Research 13(4): R81-R81, 2012

Mapping of a locus controlling cell mediated responsiveness to a tumor associated antigen to the i region of the h 2 complex. Federation Proceedings 36(3): 1202, 1977

Regulatory locus controlling autonomous expression of structural genes drm and pup contained in deo operon of escherichia coli k 12. Doklady Biological Sciences 250(1-6): 44-47, 1980

Regulatory locus controlling the autonomous expression of the structural genes drm and pup in the structure of the deo operon of Escherichia coli K-12. Doklady Akademii Nauk SSSR 250(3): 749-752, 1980

Loss of FLOWERING LOCUS C activity eliminates the late-flowering phenotype of FRIGIDA and autonomous pathway mutations but not responsiveness to vernalization. Plant Cell 13(4): 935-941, 2001

Overlap feedback an autonomous mechanism for controlling porosity during haversian bone remodeling. Biotelemetry 2(1/2): (1976), 1975

Pax3 acts cell autonomously in the neural tube and somites by controlling cell surface properties. Development 128(11): 1995-2005, 2001

Non-cell-autonomous microRNA165 acts in a dose-dependent manner to regulate multiple differentiation status in the Arabidopsis root. Development 138(11): 2303-2313, 2011

Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses. Nature Medicine 7(2): 206-214, 2001

A Leishmania major response locus identified by interval-specific congenic mapping of a T helper type 2 cell bias-controlling quantitative trait locus. Journal of Experimental Medicine 200(12): 1605-1612, 2004

The frizzled fz locus in drosophila has a non cell autonomous phenotype. Journal of Cell Biology 103(5 PART 2): 474A, 1986

Gamma delta T cell receptors confer autonomous responsiveness to the insulin-peptide B:9-23. Journal of Autoimmunity 34(4): 478-484, 2010

Autonomous inhibition of apoptosis correlates with responsiveness of colon carcinoma cell lines to ciglitazone. Plos One 9(12): E114158-E114158, 2015