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 HBsAg in vitro, whereas cells from responders proliferated vigorously. The lack of proliferative response was not due to defective antigen presentation in that MHC-identical responder and nonresponder antigen presenting 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 demonstrated that: 1) there were no detectable (1 in < 20 x 10(4) HBsAg-precursor T cells in any of the nonresponders, while in responders the 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 in response to HBsAg stimulation; 3) exogenous recombinant IL-2 did not restore the proliferative response of the T cells in HBsAg-pulsed cultures of nonresponders. These results suggest that the cellular basis for the lack of response to HBsAg is a defect in HBsAg-specific Th1-like cells; either there is an absence of the Th1 cells or cells with TCR specificity for HBsAg are present but are unresponsive to the HBsAg peptide-MHC complex (i.e., anergy or tolerance).
Chedid
M G
MG
Division of Immunogenetics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Deulofeut
H
H
Yunis
D E
DE
Lara-Marquez
M L
ML
Salazar
M
M
Deulofeut
R
R
Awdeh
Z
Z
Alper
C A
CA
Yunis
E J
EJ
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D013745:Tetanus Toxoid; D014614:Vaccines, Synthetic