DAP10 contributes to CD8(+) T cell-mediated cytotoxic effector mechanisms during Mycobacterium tuberculosis infection.
The activating C-type lectin-like receptor NKG2D, which is expressed by mouse NK cells and activated CD8 T cells, was previously demonstrated to be involved in tumor rejection and as a defense mechanism against viral and bacterial infections. Because CD8 T cells are important for protective immune responses during chronic Mycobacterium tuberculosis (Mtb) infection and represent a promising target for new vaccine strategies to prevent human pulmonary tuberculosis (TB), we studied the immune response in mice deficient for the NKG2D adapter molecule DAP10 during experimental TB. After aerosol infection, DAP10-defcient mice displayed an unimpaired recruitment, activation and development of antigen-specific CD8 T cells. Whereas the frequency of interferon-gamma-producing CD8 T cells from Mtb-infected DAP10-defcient mice was not affected, CD8 T cell-mediated cytotoxicity was significantly reduced in the absence of DAP10. The loss of cytotoxic activity in DAP10-deficient CD8 T cells was associated with an impaired release of cytotoxic granules. Together, our results suggest that during Mtb infection DAP10 is required for maximal cytolytic activity of CD8 T cells.
Infection Immunology, Research Center Borstel, Borstel, Germany.
Manuela
M
Hessmann
Alexandra
A
Rausch
Dominik
D
Rückerl
Pamela Scott
PS
Adams
Markus
M
Simon
Susan
S
Gilfillan
Marco
M
Colonna
Stefan
S
Ehlers
Christoph
C
Hölscher
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D002452:Cell Count; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*
C492355:Hcst protein, mouse; D011971:Receptors, Immunologic; D007371:Interferon-gamma