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Major histocompatibility complex class II expression on ovine T cells

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KeatingP_1995redux.pdf (26.75Mb)
Date
1995
Author
Keating, Paula
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Abstract
 
 
The expression of major histocompatibility complex (MHC) class II gene products is tightly regulated and is normally confined to professional antigen presenting cells (B cells, dendritic cells, monocytes). However many cells can be induced to express MHC class II molecules, for example human T cells do not express class II but synthesize and express high levels upon activation. In sheep, a percentage of resting T cells express class II and upon activation there is increased expression of the different MHC class II molecules (Dutia et at, 1993a). The significance of the increased class II expression after activation of T cells is unclear.
 
In this study the expression of MHC class II molecules on T cells from various immunological compartments of the sheep was examined. Monoclonal antibodies (mAbs) were characterized which react specifically with the homologues of human DRa andDQa molecules. The expression of these antigens was established on B cells and T cell subsets derived from peripheral blood, efferent lymph and afferent lymph. B cells from each of the lymphocyte sources expressed both DRa andDQa antigens. Variable expression on T cells was found. Each of the T cell subsets expressed both DR and DQ molecules at much higher levels in afferent lymph. DR expression on peripheral blood lymphocytes and efferent lymphocytes was higher than DQ on each of the T cell subsets. Afferent lymphocytes represent memory type cells and class II DR expression on these T cells may mark activation status.
 
Expression of the class II subtypes was also examined on in vivo activated T cells and correlated with expression of activation markers. Increased expression of class II molecules was coincident with the increased expression of activation markers in each of the T cell subsets with the exception of y5 cells. The lack of correlation on y5 T cells may be a reflection on the type of antigen used. Levels of DQ expression on CD4 positive cells after activation showed a more dramatic increase than levels of DR expression.
 
R expression. Cytokine profiles of concanavalin A (Con A) activated-T cells (DR positive) were examined and compared with that of DR negative T cells. The data reveal that IL-6 mRNA production correlated with DR expression. IL-6 was induced after activation of the total T cell population and was not induced in the DR negative T cells. No detectable differences in IL-4, IL-10 and ylFN mRNA profiles were observed between the total T cell population and the DR negative T cells.
 
The increased expression of class II molecules after in vivo activation coincided with the increased expression of activation markers. Correlation with activation markers did not provide further insight into the possibility that DR and DQ molecules may fulfil different functional roles whereas examination of cytokines secreted revealed that DR expression correlated with IL-6 production after Con A activation. This is indicative of a functionally distinct immunoregulatary role for DR positive T cells. The differential expression of class II molecules may fulfil distinct functions in regulating the outcome of T cell activation and the resultant effector function.
 
Using the MACS cell separation technique, a novel lymphocyte population was identified in sheep. These lymphocytes were CD3 positive suggesting they are of the T cell lineage, however they did not express markers for CD4, CD8 or y§ T cells. This null cell population represent approximately 5% of the efferent lymphocytes.
 
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http://hdl.handle.net/1842/30336
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