Expression of co-stimulatory molecules B7.1 & B7.2 on macrophages infected with various strains of Mycobacterium tuberculosis & its influence on T-cell apoptosis.

Rajavelu, P.; Das, S.D.

Indian Journal of Medical Research; 2008; 127; 388-394.

Background & objectives : Activation of T cells is mediated through two critical signals provided by activated macrophages. The first signal is triggered when T cell receptor (TCR) binds to the major histocompatibility antigen (MHC/Ag) complex. The second signal is the interaction of co-stimulatory molecules with their respective ligands on T cells for their activation and proliferation. We undertook this study to observe the modulation in B7.1 (CD80) and B7.2 (CD86) co-stimulatory molecules on Mycobacterium tuberculosis infected monocyte derived macrophages (MDM) and their role in T helper (Th1) cell apoptosis.

Methods : M. tuberculosis clinical strains (S7 and S10) and laboratory strains (H37Ra and H37Rv) were used to infect the MDMs. The modulation of apoptosis was assessed by treating T cells with anti-CD3 and anti-CD28 antibodies. The infected MDMs were co-cultured with autologous PPD pulsed T cells to ascertain the role of co-stimulatory molecules during infection.

Results : In infected MDMs, all strains on day 1 but only S7 on day 2 showed significant decrease ( P <0.05) in B7.1 expression compared to uninfected. The expression levels of B7.2 were also low on day 1 in S7, S10 and H37Ra infected MDMs. The anit-CD3 induced apoptosis in PPD pulsed T-cells showed further reduction with anti-CD28 antibodies. However, the modulation observed in B7.1 expression in infected MDMs was not reflected in T cell apoptosis in co-culture experiments.

Interpretation & conclusions : Our results confirmed the role of B7.1 in rescuing the activated T-cells from undergoing apoptosis. During infection when the expression of B7.1 is downregulated, other co-stimulatory molecules may take over its crucial role to confer protective immune response against M. tuberculosis.

Keywords: Apoptosis - B7.1 - B7.2 - co-stimulation - Mycobacterium tuberculosis

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