Abstract

Introduction and Background
Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know clinical stage accurately. There have been few attempts to use cell-mediated immune responses for diagnosing the stage of MAC.
Aims and objects
To characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium (MA)-associated antigens in different clinical stages of MAC.
Methods
47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were cultured with MA-associated antigens (named MAV0968, MAV1160, MAV1276, MAV4925), and the cytokine profiles (IFN-?, TNF-?, IL-2, IL-10, IL-13, IL-17) of CD4+/CD3+ and CD19+ cells in cultured PBMCs were analyzed by flow cytometry.
Results
The response of Th1 cytokines such as IFN-? and TNF-? against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01-0.0001, and P < 0.05-0.0001). Analysis of polyfunctional T cells suggested that IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in before-treatment (P < 0.0001 and P < 0.01-0.0001). These responses were not observed with PPD. CD19+B cells showed a response similar to that of CD4+T cells.

Conclusions
There is a characteristic cell-mediated immune response against specific antigen at each clinical stage of MAC.