Specific Lymphoproliferation, Gamma Interferon Production, and Serum Immunoglobulin G Directed against a Purified 32 kDa Mycobacterial Protein Antigen (P32) in Patients with Active Tuberculosis

Abstract

Twenty-one patients treated for active tuberculosis were examined for immune reactivity to purified protein derivative (PPD) and to a purified 32-kDa protein antigen (P32) from Mycobacterium bovis, strain BCG. Lymphoproliferation of peripheral blood leucocytes to PPD and P32 was positive in 95% and 71% of the patients respectively. A positive IFN-gamma response was detected in 62% against PPD and in 48% against P32. Low blastogenesis and IFN-gamma production were observed, especially in patients with poor general health and advanced tuberculous lesions. Twelve out of twelve (100%) of the tuberculin-positive healthy volunteers responded to PPD and P32 with mean lymphoproliferation and IFN-gamma values that were higher than in the patient group. Twelve tuberculin-negative control subjects were completely unreactive to PPD and P32 antigen. On the other hand, IgG antibodies in the serum were detected in 95% of the patients against PPD, in 77% of the patients against P32 but in none of the tuberculin-positive or negative healthy volunteers. The highest IgG levels against PPD were found in those patients with the lowest in vitro lymphoproliferation and IFN-gamma production (r = -0.54; P less than 0.05). Nonspecific interferon production following induction with Newcastle disease virus, Corynebacterium parvum, or phytohaemagglutinin was comparable in the control and patient groups. Finally, low IFN-alpha titres were detected in the serum of about 50% of the patients.

Human T‐ and B‐Cell Reactivity to the 16 kDa α‐Crystallin Protein of Mycobacterium tuberculosis

“…The negative correlation between antibody production and cell proliferation has previously been observed in human tuberculosis [14,[16][17][18]. Our data extend these observations in strongly relating the degree of antibody elevation and depression of the proliferative response to disease severity.…”

Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

“…34,35 Many attempts have been made to elucidate the natures of the TB antigens involved in stimulating protective IFN-g production. Actually, it was reported that IFN-g production specific for antigens of M. tuberculosis such as Ag85A, 35,36 Ag85B, 35,37 MTB41, 38 and ESAT-6 39 dramatically reduces in patients with active TB but not in HTR, suggesting that these antigens may be candidate protective antigens. 8 In the case of Ag85A, it was also demonstrated that the reduced production of IFN-g in response to Ag85A was significantly restored in PBMCs 35 after anti-TB chemotherapy in patients with active disease, suggesting that Ag85A-specific IFN-g response might be involved in the clinical phenotype and immunopathogenesis of human active pulmonary TB.…”

Dysregulated Production of Interferon‐γ, Interleukin‐4 and Interleukin‐6 in Early Tuberculosis Patients in Response to Antigen 85B of Mycobacterium tuberculosis

“…Much recent research has been focused on the protective immunity of the proteins of the Ag85 complex. Other studies showed that the Ag85 protein complex also induces readily elicitable cellular immune responses in cultured PBMC of most HR subjects, and in a few patients with clinically active TB [31,32]. In addition, recent studies showed that serum levels of Ag85, as complexes with fibronectin and IgG, to be significantly increased in patients with active TB, independent of skin test status [31,33,34], and these possibly play a role in systemic anergy in active TB patients by binding to and inactivating specialized T-cell fibronectin produced after antigenic stimulation [33].…”