Antigen-specific and persistent tuberculin anergy in a cohort of pulmonary tuberculosis patients from rural Cambodia

Abstract

Purified protein derivative (PPD) skin testing is used to identify persons infected with Mycobacterium tuberculosis (Mtb) and to assess cell-mediated immune responses to Mtb. However, lack of skin induration to intradermal injection of PPD or PPD anergy is observed in a subset of patients with active tuberculosis (TB). To investigate the sensitivity and persistence of PPD reactivity and its in vitro correlates during active TB disease and after successful chemotherapy, we evaluated the distribution of skin size induration after intradermal injection of PPD among 364 pulmonary TB patients in Cambodia. A subset of 25 pulmonary TB patients who had a positive skin reaction to mumps and͞or candida antigens showed persistent anergy to PPD after successful completion of TB therapy. Strikingly, in vitro stimulation of T cells from persistently anergic TB patients with mumps but not PPD resulted in T cell proliferation, and lower levels of IL-2 and IFN-␥ and higher levels of IL-10 were detected in PPD-stimulated cellular cultures from PPD-anergic as compared with PPD-reactive pulmonary TB patients. These results show that anergy to PPD is antigen-specific and persistent in a subset of immunocompetent pulmonary TB patients and is characterized by antigen-specific impaired T cell proliferative responses and a distinct pattern of cytokine production including reduced levels of IL-2.

Mycobacterium tuberculosis Recall Antigens Suppress HIV-1 Replication in Anergic Donor Cells via CD8+ T Cell Expansion and Increased IL-10 Levels

“…These individuals, all of whom achieved a chemotherapeutic and microbiological cure of TB, do not manifest a delayed-type hypersensitivity (DTH) skin response to intradermal injection of purified protein derivative (PPD), but do manifest a response to the injection of other Ags such as mumps or Candida (9,10). Concordant with these in vivo results, T cells from PPD-anergic donors display impaired responses to PPD but not to other Ags in vitro.…”

“…Concordant with these in vivo results, T cells from PPD-anergic donors display impaired responses to PPD but not to other Ags in vitro. By contrast, T cells from former TB patients with a positive skin reaction to PPD (PPD-responsive donors) in vivo respond equally to PPD and other Ags in vitro (9,10). HIV-1 infection of cells from these PPD-anergic and PPD-responsive donors thus afforded us the unique opportunity of investigating Ag-specific recall responses to MTb upon replication of HIV-1 primary isolates.…”

Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis

“…26 This notion is also supported by the lack of IL-2 and INF-g production in tetramer-reactive T cells upon peptide stimulation and is consistent with the notion of MTBantigen-specific anergy in patients with either acute or latent MTB infection. 27,28 Of note, high amount of circulating Ag85 proteins have also been incriminated to participate in antigen-specific anergy in patients with MTB infection due to the interaction of Ag85 complex with T -cell-associated fibronectins. 10,29 At this time, we are not able to link the presence of dominant HLA-B*0702 or HLA-B*0801-restricted immune responses with better response to therapy, or different patterns of disease severity.…”

The Chemokine Receptor CXCR3 Attenuates the Control of Chronic Mycobacterium tuberculosis Infection in BALB/c Mice

“…8E). Lastly, evidence exists that regulatory T cells (Tregs) modulate the host immune response to M. tuberculosis (47)(48)(49)(50). Hence, it is plausible that differential levels of Tregs and/or immunosuppressive cytokines produced by these cells (such as IL-10 and TGF␤) in the wild-type and CXCR3 Ϫ/Ϫ animals could result in different T lymphocyte responses among the two groups.…”