Natural Killer (NK) cells are an important part of innate immune defense, with a capacity to recognize virus infected and transformed cells. In contrast to T and B cells, they do not need to clonally expand, but can act directly through cytotoxicity and secretion of both cytokines and chemokines. The physiological role of NK cells during HIV infection remains unclear, although they have been shown to inhibit HIV replication in vitro, partially by the release of chemokines. NK cell function and number has been reported to be impaired in HIV-infected individuals, with partial restoration after suppression of the viral load by HAART. Moreover, expression of certain inhibitory and activating NK cell receptors correlate with viral load and/or progression to AIDS in HIV-infected patients.
The first aim of this grant application is focused on the relationship between the frequency, number, and function of NK cells early in HIV infection and the level of plasma viremia post seroconversion (virological set point), the temporal kinetics of the NK cell response in relationship to plasma HIV viral load in early HIV infection, and the effect of HIV viremia on NK cell receptor expression.
The second aim i s to determine how the time of initiation of treatment with highly active antiretroviral drug therapy (HAART) and how interleukin-2 therapy impact the frequency and function of NK cells in HIV-infected individuals. These studies will use samples taken from a cohort of HIV-infected subjects enrolled in the UCSF """"""""Options Project,"""""""" run by co-investigator Dr. F. Hecht. The studies proposed in this grant will have direct relevance for understanding the physiological role of NK cells in the pathogenesis of HIV infection, and how antiretroviral treatments and IL-2 therapy affect NK cell functions in HIV-infected subjects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI064520-02
Application #
7310279
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
2
Fiscal Year
2006
Total Cost
$398,321
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Batista, Mariana D; Tincati, Camilla; Milush, Jeffrey M et al. (2013) CD57 expression and cytokine production by T cells in lesional and unaffected skin from patients with psoriasis. PLoS One 8:e52144
Milush, Jeffrey M; López-Vergès, Sandra; York, Vanessa A et al. (2013) CD56negCD16? NK cells are activated mature NK cells with impaired effector function during HIV-1 infection. Retrovirology 10:158
Co, Elizabeth C; Gormley, Matthew; Kapidzic, Mirhan et al. (2013) Maternal decidual macrophages inhibit NK cell killing of invasive cytotrophoblasts during human pregnancy. Biol Reprod 88:155
Batista, Mariana D; Ho, Emily L; Kuebler, Peter J et al. (2013) Skewed distribution of natural killer cells in psoriasis skin lesions. Exp Dermatol 22:64-6
Ndhlovu, Lishomwa C; Lopez-Vergès, Sandra; Barbour, Jason D et al. (2012) Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood 119:3734-43
Taner, Sabrina B; Pando, Marcelo J; Roberts, Allison et al. (2011) Interactions of NK cell receptor KIR3DL1*004 with chaperones and conformation-specific antibody reveal a functional folded state as well as predominant intracellular retention. J Immunol 186:62-72
Long, Brian R; Erickson, Ann E; Chapman, Joan M et al. (2010) Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2. Immunology 129:186-96
Sun, Joseph C; Beilke, Joshua N; Lanier, Lewis L (2010) Immune memory redefined: characterizing the longevity of natural killer cells. Immunol Rev 236:83-94
Lopez-Vergès, Sandra; Milush, Jeffrey M; Pandey, Suchitra et al. (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 116:3865-74
Lanier, Lewis L; Sun, Joseph C (2009) Do the terms innate and adaptive immunity create conceptual barriers? Nat Rev Immunol 9:302-3

Showing the most recent 10 out of 31 publications