In vitro naive T cell proliferation failure predicts poor post-immunization responses to neoantigen, but not recall antigens, in HIV-infection

Immune reconstitution after HAART is incomplete, but no widely accepted method to quantify subclinical immune deficiency is available. We immunized 9 HIV-negative subjects and 29 HIV-infected patients with CD4 >= 450 cells/mu L and undetectable HIV RNA levels with 2 doses of diphtheria/tetanus toxoid (TT) and KLH, a presumed neoantigen. We quantified the response by lymphoproliferative assay, delayed-type hypersensitivity (DTH), and antibody titers up to 59 days after enrollment. We assessed T cell proliferative capacity using anti-V beta 3 and anti-V beta 5 antibody stimulation, which we herein show induced predominant proliferation of naive T cells. Subjects with detectable responses to KLH tended to exhibit greater proliferative responses to anti-V beta 3/V beta 5 stimulation; no such pattern was seen with response to TT. Several measures of in vitro T cell proliferative capacity correlated significantly with DTH and antibody responses to KLH, but not with TT responses; this association was independent of naive T cell numbers. Our results indicate that naive T cell proliferation predicts response to neo-, but not recall antigens, and suggest that it may be a meaningful reflection of in vivo immune competence in HIV-infected persons. (C) 2010 Elsevier Inc. All rights reserved.