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CD8 T cell response to Mycobacterium tuberculosis
Author(s) -
Einarsdottir Thorbjorg,
Flynn JoAnne L
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.860.2
Subject(s) - mycobacterium tuberculosis , cytotoxic t cell , biology , immune system , microbiology and biotechnology , immunology , epitope , elispot , cd8 , t cell , intracellular parasite , virology , tuberculosis , antibody , medicine , in vitro , biochemistry , pathology
The immune response against Mycobacterium tuberculosis (Mtb) is generally sufficient to contain, but not clear, the infection. Memory forms following Mtb infection and BCG vaccination, but doesn't protect from reinfection with Mtb and has limited effect on bacterial load. Our research is aimed at better understanding CD8 T cell responses to Mtb and identify host factors that prevent clearing of the bacteria. We created recombinant Mtb expressing OT1 and OT2 epitopes, recognized by CD8 and CD4 T cells respectively, which allows us to follow Ag‐specific cells during murine infection. Using tetramers, ELISpot, in vivo cytotoxicity assay and intracellular cytokine staining, OT1 responses were compared to responses against an endogenous Mtb epitope (from Rv0125, designated GAP). Our results indicate that memory cells reside in lung and lymph node after bacterial clearance and can respond faster than naïve cells. Despite this, the frequency of responding cells is not appreciably higher during memory response. This low frequency may contribute to inefficiency of the response. Additionally, most CD8 T cells are cytolytic (characterized by CD107 surface expression) or IFNg producers, but not both. Cytolysis and IFNg are both important in controlling Mtb, and the inabilityof CD8 T cells to perform both functions may contribute to persistence of bacteria in the host. Funding: NIH/NIAID AI37859‐10