title: The MHC influences NK and NKT cell functions associated with immune abnormalities and lifespan.
abstract: The lifespans of H-2 congenic mice differ significantly. The B10.AKM (H-2m) strain has a median survival time (MST) of 15 months, whereas the B10.BR (H-2k) strain has an MST of 24 months. It was previously shown that B10.AKM mice at 13-15 months of age have immunological function comparable to those of B10.BR mice at 22-26 months of age. These functions include: a low proliferative response, reduced levels of intracellular calcium release [Ca2+]i, and an increase in the frequency of memory helper T-cells (CD4+ CD44hiCD45RBlo). In this report similar deficiencies were demonstrated in B10.AKM mice at 2-4 months of age and show that activated spleen NK1.1+CD4+ T (NKT) cells from young B10.AKM mice produce a significantly higher level of IL-4 but a lower level of IFN-gamma as compared to NKT cells from B10.BR mice of the same age. Also, the cytotoxic activity of natural killer (NK) cells from spleens of young (2-4 months) as well as adult (12-16 months) B10.AKM mice is significantly lower (P < 0.01) than that of NK cells from B10.BR mice. These findings suggest that the NKT activity in young B10.AKM mice is a factor for the early onset of immune dysfunction leading to a shorter lifespan.
authors.affiliation: Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. dubey@cbr.med.harvard.edu
authors.forename: D P
authors.initials: DP
authors.lastname: Dubey
authors.forename: Z
authors.initials: Z
authors.lastname: Husain
authors.forename: E
authors.initials: E
authors.lastname: Levitan
authors.forename: D
authors.initials: D
authors.lastname: Zurakowski
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: S
authors.initials: S
authors.lastname: Younes
authors.forename: C
authors.initials: C
authors.lastname: Coronell
authors.forename: D
authors.initials: D
authors.lastname: Yunis
authors.forename: E J
authors.initials: EJ
authors.lastname: Yunis
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020013:Calcium Signaling; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000235:genetics; D005260:Female; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008136:Longevity / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma