title: Early activated Th-1 type and dominantly diverse natural killer T (CD3⁺CD161⁺Vα24⁻) cells in bone marrow among visceral leishmaniasis patients.
abstract: Lipid antigens of Leishmania donovani-like lipophosphoglycans (LPG) are demonstrated to be a potent ligand for natural killer T (NKT) cell activation. Little is known about the phenotype or function of these cells and their trafficking pattern to the bone marrow (BM) of visceral leishmaniasis (VL) patients. Their precise role in humans still requires pathological validation. The study included 42 parasitologically confirmed patients (mean age 24.80±16.26 years; range 3-70 years; 25 males and 17 females), 33 healthy contact subjects (family/non-family members) and normal BM specimens (NBM; n=9). Enumeration of NKT cells and quantification of parasites (before and after therapy) were performed for the recruited patients. Results established that non-CD1d restricted, diverse cells are the dominant population among resident but not enriched NKT (CD3⁺CD161⁺) cells at the disease site (BM). Expression profiles for various markers are indicative of their early activated (CD69⁺, CD62L(low), CD11a(high)) CCR5⁺ phenotype at the BM. Functionally, BM-derived NKT cells were dominantly producing IFN-γ in response to L. donovani antigen in vitro. Given these observations, these data indicate that CD3⁺CD161⁺ diverse NKT cells are heterogeneous in function and of the dominant Th-1 phenotype at the disease site.
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institutes of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Ambak Kumar
authors.initials: AK
authors.lastname: Rai
authors.forename: Chandreshwar Prasad
authors.initials: CP
authors.lastname: Thakur
authors.forename: Tulika
authors.initials: T
authors.lastname: Seth
authors.forename: Dipendra Kumar
authors.initials: DK
authors.lastname: Mitra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000737:chemistry / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology*; D055815:Young Adult
chemical_list: D017252:CD3 Complex; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011948:Receptors, Antigen, T-Cell; C528689:Valpha24 protein, human; D007371:Interferon-gamma