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.