Cellular immune responses to Mycobacterium tuberculosis in a patient with Takayasu's arteritis.

INTRODUCTION: Takayasu's arteritis (TA) is a disease of unknown aetiology, characterized histologically by an inflammatory cell infiltrate that affects all layers of the arterial wall. Its association with tuberculosis (TB) was described 50 years ago, based on the presence of Langhan's giant cells and granulomas similar to those found in tuberculous lesions. The presence of TB in patients with TA well as been reported in several studies as well as a positive tuberculous response, but these associations could be fortuitous in countries where TB is endemic. Recent studies have shown that patients with TA have a heightened humoral response to mycobacterial antigens including the 65 kDa fraction, a heat shock protein (HSP) that has also been found to be expressed in the arterial wall of patients with TA. The purpose of this study was to determine lymphoproliferative response and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) stimulated by live Mycobacterium tuberculosis (Mtb) H37Rv and a panel of mycobacterial antigens, in the hope of contributing to a better understanding of the cellular immune responses to Tuberculosis in Takayasu's arteritis. MATERIAL AND METHODS: Standard lymphoproliferation tests and IFN-gamma determination (ELISA) were performed in a 47-year old black man who fulfilled criteria for TA and 10 healthy controls, BCG vaccinated, Mantoux positive. The following were used: Mtb H37Rv, Purified Protein Derivative (PPD), purified 30 kDa, recombinant M. bovis BCG 10 kDa, 38 kDa, 65 kDa, 70 kDa, Short Term-Culture Filtrate Proteins (ST-CFP), Mid Term-Culture Filtrate Proteins (MT-CFP) obtained from H37Rv and phytohemaglutinin (PHA) as mitogen for positive control. RESULTS: PBMC from the patient with TA when compared to the mean values of the 10 healthy donors showed decreased proliferation in response to all antigens, with the exception of 65 kDa. The TA patient showed a similar pattern of IFN-gamma production to that obtained with control donors, with the exception of higher IFN-gamma production in response to ST-CFP and MT-CFP. CONCLUSIONS: We have shown reactivity of peripheral lymphocytes to HSP 65 kDa and a trend towards higher production of IFN-gamma in response to ST-CFP and MT-CFP in a patient with TA. These facts, together with the already established heightened humoral response, strengthens the association between TB and TA. However, HSP 65 kDa is not specific to TB and we conclude that similar studies using lymphocytes obtained from the arterial wall of TA patients may help to clarify the role of mycobacterial infection in Takayasu's arteritis.

[Cellular immune response to mycobacterial antigens]. / Respostas imuno-celulares a antigénios micobacterianos.

The authors studied the immunological response before and after beginning anti-tuberculous therapy, of a previously health, HIV negative, 22 year old black male, from the Republic of Cape Verde. The patient had multiple vertebral bony lesions associated to subcutaneous abscesses. As immunological markers of antigen recognition, we measured blastogenic and cytotoxic responses and gamma-IFN secretion towards 30 kD, 65 kD, filtrate proteins of M. tuberculosis, M. tuberculosis (H37Rv) and PPD cultures. To characterise the role of cytokines during infection, expression of mRNA for gamma-IFN, IL-4 and IL-10 was also analysed. A slight increase of lymphocyte proliferation and gamma-IFN production was seen in response to purified protein derivative (PPD) and short term culture filtrate proteins (ST-CFP), after one month of therapy. More significant, was the increase in M. tuberculosis and PPD-specific cytolytic T lymphocyte response after one one month of treatment. After 6 months of treatment, blastogenic and cytotoxic responses and gamma-IFN production were considerably higher toward the antigen panel. The CD4/CD8 ratio increased from 0.7 to 1.4 after treatment. We observed that ST-CFP and MT-CFP induced increasingly higher lymphoproliferation and gamma-IFN production, confirming their role in the protective immune responses to M. tuberculosis. The reduced immune responses in the peripheral blood of this patient probably reflect a high activity in the local sites of infection. This case of disseminated tuberculosis infection maybe related to nutritional or social factors or may represent an example of reduced in ate resistance against tuberculosis infection.