DEFECTS IN ANTIGEN-DRIVEN LYMPHOCYTE-RESPONSES IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) ARE DUE TO A REDUCTION IN THE NUMBER OF ANTIGEN-SPECIFIC CD4-CELLS( T)

T cells from patients with CVID have defects that may relate to the fa ilure in vivo of B cell production of antibodies, Antigen-driven respo nses of T cells from CVID patients and normal subjects have been asses sed by measuring DNA synthesis in vitro. Low density cells enriched fo r antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T eels. Overall, T cell s from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 wa s within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of mon ocytes. Depletion of CD8(+) cells also failed to restore the mean PPD response of CVID CD4(+) T cells. Limiting dilution analysis showed tha t in CVID there was a reduced frequency of antigen-specific cells with in the T cell preparations. The mean frequency of the PPD-specific T c ells in cultures from patients vaccinated with bacille Calmette-Guerin (BCG) was reduced to 1 in 109 000 T cells compared with I in 18 600 T cells in BCG-vaccinated normal donors. These data show that the reduc ed PPD-specific response in CVID is due to a partial peripheral loss o f antigen-specific cells.