ACCESSORY FUNCTION FOR NK1. 1+ NATURAL KILLER CELLS PRODUCING INTERFERON-γ IN XENOSPECIFIC CYTOTOXIC T LYMPHOCYTE …

MJ Smyth, JM Kelly - Transplantation, 1999 - journals.lww.com
MJ Smyth, JM Kelly
Transplantation, 1999journals.lww.com
Background. We have previously demonstrated that xenospecific cytotoxic T lymphocyte
(CTL) differentiation requires accessory function by NK1. 1+ cells, yet the mechanism by
which NK1. 1+ cells support CTL generation had not been elucidated. Methods. An
established model in which mice generate a strong local popliteal lymph node CTL
response to footpad immunizations with human tumor cells was used. Mice depleted of NK1.
1+ cells fail to mount a maximal xenospecific CD8+ CTL response. The xenospecific CTL …
Abstract
Background.
We have previously demonstrated that xenospecific cytotoxic T lymphocyte (CTL) differentiation requires accessory function by NK1. 1+ cells, yet the mechanism by which NK1. 1+ cells support CTL generation had not been elucidated.
Methods.
An established model in which mice generate a strong local popliteal lymph node CTL response to footpad immunizations with human tumor cells was used. Mice depleted of NK1. 1+ cells fail to mount a maximal xenospecific CD8+ CTL response. The xenospecific CTL response in anti-NK1. 1 monoclonal antibody-depleted mice could be completely restored if mice were coinoculated with human tumor cells (the xenoantigen) and xenoantigen-stimulated syngeneic natural killer (NK) cells from wild-type or perforin-deficient mice. By contrast, NK1. 1+ cells from interferon-γ-deficient mice did not restore the maturation of xenospecific CTL in anti-NK1. 1 monoclonal antibody-treated mice. Depletion of NK1. 1+ cells in vivo from both wild-type and Jα281-deficient mice (which lack Vα14 NK1. 1+ T cells) abrogated the generation of xenospecific CTL, however, untreated Jα281-deficient mice mounted a normal xenogeneic response.
Conclusions.
These data indicate that local NK cell production of interferon-γ at the site of challenge is an important stimulus for generating xenospecific CTL in local draining lymph nodes and that Vα14 NK T cells play little or no regulatory function in this response.
Lippincott Williams & Wilkins