6.833333
#19
ACUTE MURINE GRAFT-VS.-HOST DISEASE (GVHD) INDUCED USING NKT CELL KNOCKOUT (J281^-/-) DONORS.
Cynthia (Cindy) A. Ellison PhD ^1,2, Masaru Taniguchi MD, PhD ³ and John G. Gartner MD, CM FRCP(C) ^1,4. ¹ Dept. of Pathology, University of Manitoba, Winnipeg, MB, Canada ; ² Manitoba Blood & Marrow Transplant Program, CancerCare Manitoba, Winnipeg, MB, Canada ; ³ RIKEN Research Center for Allergy and Immunology, Yokohama, Japan and ⁴ Dept. of Immunology, University of Manitoba, Winnipeg, MB, Canada .

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Using a Parental StrainF₁-hybrid model, we previously showed that cytotoxic cells expressing both NK cell markers such as NK1.1 and ASGM₁ as well as T cell markers such as Thy-1 and TCR become activated during the development of acute GVHD. We recently induced GVH reactions in the C57BL/6(C57BL/6 x DBA/2)F₁-hybrid model using J281^-/- donor mice that are deficient in a CD1-restricted subset of NKT cells, which express an TCR with an invariant V14 (V14i). Recipients of grafts from J281^-/- donors were not protected from either the morbidity or severe wasting syndrome that develops in recipients of wild-type grafts. The percentages of CD4⁺ and CD8⁺ cells in grafts from J281^-/- donors were not significantly different from those seen in grafts from wild-type donors. When we compared the levels of IFN-, IL-4, IL-5 and IL-13 in recipients of grafts from either wild-type or J281^-/- donors on days 4, 8 and 15 post-induction, the only significant difference was a higher level of IL-5 in the latter group on day 4 (p<0.002). LPS-induced TNF release, a response that is consistently seen recipients of grafts from wild-type donors, was also seen in recipients of grafts from J281^-/- donors. These findings indicate that the V14i⁺ subset of donor NKT cells is not required for the development of acute GVHD in this murine model. They do not, however, preclude the possibility that other subsets of NKT cells might be involved.