β-cell antigen-specific CD56+ NKT cells from type 1 diabetic patients:: Autoaggressive effector T cells damage human CD56+ β cells by HLA-restricted and non-HLA-restricted pathways

Studies of type I diabetes indicate that autoaggressive T cells specific to beta-cell antigens, reaching certain threshold levels, may play critical roles in the development of the disease. Flow cytometric analyses found that autoreactive T-cell lines from patients induced X beta-cell antigens consisted of four major subsets (CD4(+) CD56(-), CD4(+)CD56(+) CD8(+) CD56(-), and CD8(+)CD56(+) and that CD56(+) NKT cells might be derived from CD56(-) T cells. Moreover, the proportion of CD56(+) NKT cells in the T-cell lines was influenced by time course of repeated antigen stimulation. beta-cell antigen-specific CD56(+) NKT (CD4(+) or CD8(+)) cells were more aggressive (HLA-restricted and -unrestricted) effector cells lysing target cells such as K562, Jurkat, P815 plus anti-CD3 antibody, and autologous B cells sensitized by beta-cell peptides, when compared with their CD56- counterparts. beta-cell antigen-specific CD4(+) CD56(+) NKT cells showed non-HLA-restricted cytotoxicity to human P cells, insulinoma cell line CM, and to islet cell lines TRM-6 and HP62 expressing CD56 but not to four CD56(-) pancreatic cell lines of nonislet origin. The CD4(+) CD56(+) NKT cells showed stronger cytotoxicity to CM, TRM-6 and HP62 cells than did CD4(+) CD56(-) T cells. Moreover, isotope-unlabelled CD56(+) cells and anti-CD56 antibodies were able to inhibit cytotoxicity of CD4(+)CD56(+) NKT to CD56(+) target cells. These results suggest that CD56(+) NKT cells are aggressive cytotoxic cells to beta cells and that CD56 expression might be associated with the aggressiveness of effector T cells and the Susceptibility of target cells. (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc.