DEFECT IN TH1-LIKE CELLS OF NONRESPONDERS TO HEPATITIS-B VACCINE

Peripheral blood lymphocytes from nonresponders to hepatitis B vaccine (HBsAg) failed to undergo a proliferative response to recombinant HBs Ag in vitro, whereas cells from responders proliferated vigorously. Th e lack of proliferative response was not due to defective antigen pres entation in that MHC-identical responder and nonresponder antigen pres enting cells were equally effective in stimulating responder T cells. Nonresponder T cells did not proliferate in response to antigen-pulsed MHC identical responder antigen presenting cells. The present study d emonstrated that: 1) there were no detectable (1 in <20 X 10(4)) HBsAg -precursor T cells in any of the nonresponders, while in responders th e frequency of HBsAg-precursor T cells ranged from 1 in 3.2 X 10(3) to 1 in 40 X 10(3); 2) nonresponder cell cultures did not secrete IL-2 i n response to HBsAg stimulation; 3) exogenous recombinant IL-2 did not restore the proliferative response of the T cells in HBsAg-pulsed cul tures of nonresponders. These results suggest chat the cellular basis for the lack of response to HBsAg is a defect in HBsAg-specific Th1-li ke cells; either there is an absence of the Th 1 cells or cells with T CR specificity for HBsAg are present but are unresponsive to the HBsAg peptide-MHC complex (i.e., anergy or tolerance), (C) American Society for Histocompatibility and Immunogenetics, 1997, Published by Elsevie r Science Inc.