CD1d-restricted NKT cells contribute to the age-associated decline of T cell immunity.
NKT cells are known to regulate effector T cell immunity during tolerance, autoimmunity, and antitumor immunity. Whether age-related changes in NKT cell number or function occur remains unclear. Here, we investigated whether young vs aged (3 vs 22 mo old) mice had different numbers of CD1d-restricted NKT cells and whether activation of NKT cells by CD1d in vivo contributed to age-related suppression of T cell immunity. Flow cytometric analyses of spleen and LN cells revealed a 2- to 3-fold increase in the number of CD1d tetramer-positive NKT cells in aged mice. To determine whether NKT cells from aged mice differentially regulated T cell immunity, we first examined whether depletion of NK/NKT cells affected the proliferative capacity of splenic T cells. Compared with those from young mice, intact T cell preparations from aged mice had impaired proliferative responses whereas NK/NKT-depleted preparations did not. To examine the specific contribution of NKT cells to age-related T cell dysfunction, Ag-specific delayed-type hypersensitivity and T cell proliferation were examined in young vs aged mice given anti-CD1d mAb systemically. Compared with young mice, aged mice given control IgG exhibited impaired Ag-specific delayed-type hypersensitivity and T cell proliferation, which could be significantly prevented by systemic anti-CD1d mAb treatment. The age-related impairments in T cell immunity correlated with an increase in the production of the immunosuppressive cytokine IL-10 by splenocytes that was likewise prevented by anti-CD1d mAb treatment. Together, our results suggest that CD1d activation of NKT cells contributes to suppression of effector T cell immunity in aged mice.
Faunce
Douglas E
DE
Department of Surgery, Loyola University Medical Center, and Burn and Shock Trauma Institute, Maywood, IL 60153, USA. dfaunce@lumc.edu
Palmer
Jessica L
JL
Paskowicz
Kelly K
KK
Witte
Pamela L
PL
Kovacs
Elizabeth J
EJ
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis / Q000502:physiology*; D055610:Antigens, CD1d; D000950:Antigens, Ly / Q000032:analysis; D005260:Female; D016753:Interleukin-10 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D055630:Receptors, NK Cell Lectin-Like; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000950:Antigens, Ly; D037181:Lectins, C-Type; D055630:Receptors, NK Cell Lectin-Like; D016753:Interleukin-10