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Background/aims: Mucosa-associated T-lymphocyte (MAIT) cells that are selectively accumulated in the intestinal mucosa may be involved in immune regulation. MAIT cells are determined by their Vα7.2-Jα33 (human)/Vα19-Jα33 (mice) invariant chain. The encoding DNA sequences of Human Jα33 and mouse Jα33 are identical. In order to study the role of MAIT cells in IBD we produced anti-Jα33 antibody to detect MAIT cells in TNBS induced IBD models., Methodology: Colitis was induced by TNBS in male BALB/c mice. Jα33+MAIT cells from normal mice were transferred into TNBS induced mice as donors. Colitis severity was evaluated clinically and histologically, under the condition of transferred Jα33+MAIT cells., Results: The mRNA and protein expression levels of MAIT aTCR in the colonic mucosa were decreased after TNBS administration; Jα33+MAIT cells were aggregated in spleen after TNBS administration. The disease activity index (DAI) which was determined by weight loss, stool consistency and intestinal bleeding, increased after TNBS administration. Transferred Jα33+MAIT cells significantly degrade the increase in the disease activity index scores., Conclusions: Taken together, the results indicated that the aggregation of Jα33+MAIT cells in intestinal mucosa improved TNBS-induced colitis. We conclude that Jα33+MAIT cells play a protective role in TNBS induced intestinal inflammation.

The underlying mechanism of the protective and suppressive role of NKT cells in human tumor immunosurveillance remains to be fully elucidated. We show that the frequencies of CD8(+) NKT cells in patients with EBV-associated Hodgkin's lymphoma or nasopharyngeal carcinoma are significantly lower than those in healthy EBV carriers. These CD8(+) NKT cells in tumor patients are also functionally impaired. In human-thymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-gamma-biased CD8(+) NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Th1 bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Interleukin-4-biased CD4(+) NKT cells are predominately generated in unchallenged chimeras. These cells are noncytotoxic, drive syngeneic T cells into a Th2 bias, and do not affect T-cell cytotoxicity. In humanized xenogeneic tumor-transplanted hu-thym-SCID chimeras, adoptive transfer with EBV-induced CD8(+) NKT cells significantly suppresses tumorigenesis by EBV-associated malignancies. EBV-induced CD8(+) NKT cells are necessary and sufficient to enhance the T-cell immunity to EBV-associated malignancies in the hu-thym-SCID chimeras. CD4(+) NKT cells are synergetic with CD8(+) NKT cells, leading to a more pronounced T-cell antitumor response in the chimeras cotransferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD8(+) NKT cells could be a useful strategy in management of EBV-associated malignancies.

The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19(+)CD5(+) B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19(+)CD5(+) B cells did not change. CD19(+)CD5(+) B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-gamma, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19(+)CD5(+) B cells play a prominent role in the pathogenesis of primary IgA nephropathy.

A subset of naturally formed sphingosine-1-phosphate receptor 1 (S1P1)-bearing CD8(+)CD44(+)CCR7(+) memory T cells has been identified in transplant recipient BALB/c (H-2(d)) mice. The frequency of this subset of memory T cells is significantly increased in the spleen, lymph nodes and skin grafts in the recipient BALB/c mice during acute skin allograft rejections. The immune-reconstitution with CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells facilitates acute skin allograft rejection in SCID mice. Being Th1-polarized and cytotoxic, CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells proliferate and differentiate immediately into effectors upon encountering allo-antigens. A siRNA against S1P1 inhibits CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cell-mediated acute skin allograft rejection in SCID mice by means of knocking-down S1P1-expression. CCL21 mutant (CCL21-DeltaCT) has been used to compete with wild-type CCL21 in the course of binding to CCR7. Combined administration of siRNA S1P1 and CCL21-DeltaCT significantly prolongs the survival of skin allograft in the recipient BALB/c mice by means of inhibiting accumulation of CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells in the spleen and the skin grafts. Our data provide direct evidence that S1P1 and CCR7 are involved in the proliferation and trafficking of CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells. S1P1 may serve as a functional marker for CD8(+)CD44(+)CCR7(+) memory T cells. Targeting CD8(+)CD44(+)CCR7(+)S1P1(+) T cells may be a useful strategy to prolong the survival of allograft transplant.