RESUMO
The prognosis after hematopoietic cell transplantation (HCT) for the treatment of leukemia or lymphoma in humans is influenced by donor-derived natural killer (NK) cells, which enhance the graft-versus-leukemia (GVL) effect. Such alloreactive killer cells can be generated in vivo after HCT if the donor expresses killer cell immunoglobulin-like receptors (KIRs), such as KIR2DL1, KIR2DL2/3, or KIR3DL1, for which the recipient lacks HLA class I ligands. We studied effector cells from 22 KIR/HLA-ligand mismatched and 14 KIR/HLA-ligand matched, primarily HLA-matched patient-donor pairs after allogeneic HCT. A novel 8-color flow cytometry panel allowed us to characterize effector-cell populations without "broadly reactive" inhibitory receptors such as CD94/NKG2A or LIR1. The numbers of such NKG2A(-) LIR1(-) NK cells increased following HCT in patients transplanted by KIR/HLA-ligand mismatched grafts, compared to KIR/HLA-ligand matched grafts, and in patients transplanted from donors of the A/B, compared to A/A, KIR haplotypes. NKG2A(-)LIR1(-) NK cells expressing only those inhibitory KIRs for which the patient had no HLA class I ligands could be stimulated by HLA class I-deficient cells to express CD107a. Thus, NKG2A(-)LIR1(-) NK cells may be important GVL effector cells following HCT, even in patients transplanted from HLA-matched donors.
Assuntos
Antígenos CD/imunologia , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/imunologia , Leucemia/imunologia , Linfoma/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Receptores Imunológicos/imunologia , Adulto , Idoso , Antígenos CD/biossíntese , Feminino , Citometria de Fluxo/métodos , Antígenos HLA/biossíntese , Humanos , Leucemia/terapia , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/biossíntese , Prognóstico , Receptores Imunológicos/biossíntese , Subpopulações de Linfócitos T/imunologiaRESUMO
In animal models autoreactive CD8(+) T cells are crucial in the development of type 1 diabetes (T1D); however, their role in human T1D is still not known. To address the role of CD81 T cells we performed a pilot study by investigating CD8(+) T cell-mediated cytokine secretion after in vitro stimulation with 94 preproinsulin (PPI) peptides. We were able to show that CD8(+) T cells contribute to a strong IFNgamma reactivity against PPI in human T1D. Further investigations defining epitope specificity, cytokine secretion, and cytotoxic capacity are important to clarify their role in T1D development.