Loss of Effector and Anti-Inflammatory Natural Killer T Lymphocyte Function in Pathogenic Simian Immunodeficiency Virus Infection

PLoS Pathogens

Simon Yue¹  Mark A. Exley¹  Namita Rout²  R. Paul Johnson²  Amitinder Kaur²  David O'Connor³  Justin Greene³  James G. Else⁴ 

[1] Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America;New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America;Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America

关键词: Macaque;    Lymphocytes;    SIV;    Cytokines;    Rhesus monkeys;    T cells;    Immune activation;    Blood;   

DOI  :  10.1371/journal.ppat.1002928

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Chronic immune activation is a key determinant of AIDS progression in HIV-infected humans and simian immunodeficiency virus (SIV)-infected macaques but is singularly absent in SIV-infected natural hosts. To investigate whether natural killer T (NKT) lymphocytes contribute to the differential modulation of immune activation in AIDS-susceptible and AIDS-resistant hosts, we compared NKT function in macaques and sooty mangabeys in the absence and presence of SIV infection. Cynomolgus macaques had significantly higher frequencies of circulating invariant NKT lymphocytes compared to both rhesus macaques and AIDS-resistant sooty mangabeys. Despite this difference, mangabey NKT lymphocytes were functionally distinct from both macaque species in their ability to secrete significantly more IFN-γ, IL-13, and IL-17 in response to CD1d/α-galactosylceramide stimulation. While NKT number and function remained intact in SIV-infected mangabeys, there was a profound reduction in NKT activation-induced, but not mitogen-induced, secretion of IFN-γ, IL-2, IL-10, and TGF-β in SIV-infected macaques. SIV-infected macaques also showed a selective decline in CD4+ NKT lymphocytes which correlated significantly with an increase in circulating activated memory CD4+ T lymphocytes. Macaques with lower pre-infection NKT frequencies showed a significantly greater CD4+ T lymphocyte decline post SIV infection. The disparate effect of SIV infection on NKT function in mangabeys and macaques could be a manifestation of their differential susceptibility to AIDS. Alternately, these data also raise the possibility that loss of anti-inflammatory NKT function promotes chronic immune activation in pathogenic SIV infection, while intact NKT function helps to protect natural hosts from developing immunodeficiency and aberrant immune activation.

【 授权许可】

CC BY