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Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes.

Lee CK, Gimeno R, Levy DE - J. Exp. Med. (1999)

Bottom Line: Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation.We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling.Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.

ABSTRACT
Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling. Surprisingly, an IFN-independent requirement for STAT1 was also found, specifically in T lymphocytes, where MHC class I expression was not fully accounted for by IFN signaling. This IFN-independent pathway maintained tyrosine phosphorylation of STAT1 in T but not B lymphocytes even in the absence of IFN receptors. Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells. These loss of function studies demonstrate an essential role of endogenous IFN and activated STAT1 for constitutive MHC class I expression in normal mice and define IL-7-dependent but IFN-independent regulation of STAT1 restricted to T lymphocytes.

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Reduced surface expression of MHC class I antigens in different subsets of STAT1−/− lymphocytes. Freshly isolated lymphocytes from thymi (A) or lymph nodes (B) of wild-type (dashed lines), STAT1−/− (bold lines), or (AR+GR)−/− (thin lines) mice were triple stained with CD4–TC, CD8–PE, and MHC class I–FITC, followed by FACS™ analysis. CD4−CD8− lymphocytes from lymph nodes were regarded as B cells.
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Figure 4: Reduced surface expression of MHC class I antigens in different subsets of STAT1−/− lymphocytes. Freshly isolated lymphocytes from thymi (A) or lymph nodes (B) of wild-type (dashed lines), STAT1−/− (bold lines), or (AR+GR)−/− (thin lines) mice were triple stained with CD4–TC, CD8–PE, and MHC class I–FITC, followed by FACS™ analysis. CD4−CD8− lymphocytes from lymph nodes were regarded as B cells.

Mentions: The greater reduction of class I heavy and light chain mRNA in STAT1−/− cells relative to IFN receptor mutants (Fig. 2) suggested that STAT1 may be important even in the absence of IFN. To further examine the role of constitutive IFN signaling in MHC expression patterns on different subsets of lymphocytes, we compared MHC class I antigen levels on lymphocytes from mice devoid of IFN signaling by combined loss of receptors for both IFN-α and IFN-γ (Fig. 4). As noted above, higher levels of MHC class I expression were detected on lymphocytes from peripheral organs than on thymocytes. Different subsets of T lymphocytes also displayed different levels of class I. CD4+CD8+ DP thymocytes expressed very limited amounts of surface MHC class I compared with CD4−CD8− DN or CD4− CD8+ and CD4+CD8− SP thymocytes (Table ). In peripheral organs, the levels of MHC class I on both CD4 and CD8 T lymphocytes were further elevated compared with those of SP thymocytes.


Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes.

Lee CK, Gimeno R, Levy DE - J. Exp. Med. (1999)

Reduced surface expression of MHC class I antigens in different subsets of STAT1−/− lymphocytes. Freshly isolated lymphocytes from thymi (A) or lymph nodes (B) of wild-type (dashed lines), STAT1−/− (bold lines), or (AR+GR)−/− (thin lines) mice were triple stained with CD4–TC, CD8–PE, and MHC class I–FITC, followed by FACS™ analysis. CD4−CD8− lymphocytes from lymph nodes were regarded as B cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195695&req=5

Figure 4: Reduced surface expression of MHC class I antigens in different subsets of STAT1−/− lymphocytes. Freshly isolated lymphocytes from thymi (A) or lymph nodes (B) of wild-type (dashed lines), STAT1−/− (bold lines), or (AR+GR)−/− (thin lines) mice were triple stained with CD4–TC, CD8–PE, and MHC class I–FITC, followed by FACS™ analysis. CD4−CD8− lymphocytes from lymph nodes were regarded as B cells.
Mentions: The greater reduction of class I heavy and light chain mRNA in STAT1−/− cells relative to IFN receptor mutants (Fig. 2) suggested that STAT1 may be important even in the absence of IFN. To further examine the role of constitutive IFN signaling in MHC expression patterns on different subsets of lymphocytes, we compared MHC class I antigen levels on lymphocytes from mice devoid of IFN signaling by combined loss of receptors for both IFN-α and IFN-γ (Fig. 4). As noted above, higher levels of MHC class I expression were detected on lymphocytes from peripheral organs than on thymocytes. Different subsets of T lymphocytes also displayed different levels of class I. CD4+CD8+ DP thymocytes expressed very limited amounts of surface MHC class I compared with CD4−CD8− DN or CD4− CD8+ and CD4+CD8− SP thymocytes (Table ). In peripheral organs, the levels of MHC class I on both CD4 and CD8 T lymphocytes were further elevated compared with those of SP thymocytes.

Bottom Line: Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation.We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling.Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.

ABSTRACT
Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling. Surprisingly, an IFN-independent requirement for STAT1 was also found, specifically in T lymphocytes, where MHC class I expression was not fully accounted for by IFN signaling. This IFN-independent pathway maintained tyrosine phosphorylation of STAT1 in T but not B lymphocytes even in the absence of IFN receptors. Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells. These loss of function studies demonstrate an essential role of endogenous IFN and activated STAT1 for constitutive MHC class I expression in normal mice and define IL-7-dependent but IFN-independent regulation of STAT1 restricted to T lymphocytes.

Show MeSH
Related in: MedlinePlus