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


CONCLUSIONS
Our results confirmed the role of B7.1 in rescuing the activated Tcells 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.
Rajavelu
Priya
P
Tuberculosis Research Centre ICMR, Chennai, India.
Das
Sulochana D
SD
D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human