EVIDENCE FOR EARLY TH2 T-CELL PREDOMINANCE IN XENOREACTIVITY

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.