Two distinct subsets of CD4+ Th lymphocytes have been characterized by
their cytokine profiles: Th 1 (TH1) and Th 2 (TH2). While TH1 cells p
redominate in cell-mediated responses, TH2 cells support the humoral r
esponse. We have examined the mRNA cytokine profile of normal mouse ly
mphocytes in response to alloantigen versus xenoantigen (rat) in MLC,
and present evidence to suggest that early in proliferative responses,
alloreactivity is dominated primarily by TH1-type lymphocytes, while
xenoreactivity is predominantly TH2. Normal mouse lymphocyte-respondin
g cells were cultured in a one-way MLR with either allo or xeno antige
n and examined for production of mRNA for cytokines characteristically
produced by TH1 (IL-2, IFN-gamma) or TH2 (IL-4, IL-10) cells. Semiqua
ntitative reverse transcription-polymerase chain reaction analysis was
performed for mouse IL-2, IL-4, IL-10, and IFN-gamma mRNA. In the mou
se anti-rat xeno response, mRNA for TH2 gene products were upregulated
, with greater levels of IL-4 and IL-10 at 24 and 48 hr when compared
with controls. In contrast, upregulation of mRNA for TH1 gene products
occurred in the mouse anti-mouse allo response, with higher levels of
IL-2 and IFN-gamma at 24 and 48 hr. In the anti-xeno response, upregu
lation of all 4 cytokines occurred by day 4 and peak levels of mRNA fo
r all cytokines examined were 2-3 times that seen for the peak anti-al
logeneic response. These data suggest that early xenorecognition may d
iffer from allorecognition by differential activation of the TH2 subse
t. A better understanding of the balance between Th subset function an
d cytokine profile in allo and xeno reactivity may allow a more target
ed and specific approach to control the early events in xenograft reje
ction.