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PD‐L1 interaction limits excessive Th1 effector function during Mycobacterium tuberculosis infection
Author(s) -
Barber Daniel L.,
Antonelli Lis R.,
Feng Carl G.,
Sharpe Arlene H.,
Freeman Gordon J,
Sher Alan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.663.20
Subject(s) - t cell , mycobacterium tuberculosis , biology , immunology , effector , splenocyte , chronic infection , blockade , spleen , virology , immune system , tuberculosis , microbiology and biotechnology , medicine , receptor , biochemistry , pathology
Mycobacterium tuberculosis establishes a persistent infection despite a T cell response that contains but does not clear the pathogen. The B7 family member PDL1 has been shown to play a major role in regulating T cell responses during chronic viral infection. Here we investigate its role in regulating T cell function during murine Mtb infection. PD‐1 was upregulated on T cells in lung and spleen after low‐dose aerosol infection and PDL1 was markedly increased on multiple cell types. αPDL1 administration from wk10–14 had no effect on bacterial control but led to a 2–3 fold reduction in the number of IFNγ+ T cells. Furthermore, in contrast to previous reports with virus specific T cells, PDL1 blockade during culture of splenocytes from Mtb infected mice reduced T cell proliferation and triggered enhanced apoptosis. In the presence of αIFNγ neutralizing mAb or aminoguanidine, however, in vitro PDL1 blockade enhanced CD4 T cell division suggesting that this pathway protects T cells from suppression by IFNγ and nitric oxide by limiting their production. Moreover in recent experiments Mtb infected PDL1 KO mice were found to display acute mortality succumbing by day 31 post‐exposure. Taken together these data suggest that a major function of PDL1 in Mtb infection may be to limit potentially host detrimental Th1 responses.