title: Expansion of CD8+ T cells lacking Sema4D/CD100 during HIV-1 infection identifies a subset of T cells with decreased functional capacity.
abstract: Sema4D, also known as CD100, is a constitutively expressed immune semaphorin on T cells and NK cells. CD100 has important immune regulatory functions that improve antigen-specific priming by antigen-presenting cells, and can also act as a costimulatory molecule on T cells. We investigated the consequence of HIV-1 infection on CD100 expression by T cells, and whether CD100 expression signifies functionally competent effector cells. CD100 expression on T cells from healthy individuals was compared with HIV-1-infected subjects including elite controllers, noncontrollers, and patients receiving antiretroviral therapy. The frequency and fluorescence intensity of CD100 on CD8(+) and CD4(+) T cells were decreased during HIV-1 infection. Furthermore, the absolute number of CD100-expressing CD8(+) T cells was positively associated with the magnitude of HIV-1-specific T-cell responses. CD8(+) T cells lacking CD100 expression were functionally impaired and present in increased numbers in HIV-1-infected individuals. The number of CD100(-)CD8(+) T cells positively correlated with T-cell immunosenescence, immune activation, and viral load. Loss of CD100 expression appears to result from direct antigen stimulation, as in vitro cytokine exposure and viral replication did not significantly impact CD100 expression. These data suggest that loss of CD100 expression probably plays an important role in dysfunctional immunity in HIV-1 infection.
authors: Division of Experimental Medicine, Department of Medicine, University of California–San Francisco, USA. erikssonemy@gmail.com
authors: Emily M
authors: EM
authors: Eriksson
authors: Jeffrey M
authors: JM
authors: Milush
authors: Emily L
authors: EL
authors: Ho
authors: Mariana D
authors: MD
authors: Batista
authors: Sara J
authors: SJ
authors: Holditch
authors: Chris E
authors: CE
authors: Keh
authors: Philip J
authors: PJ
authors: Norris
authors: Sheila M
authors: SM
authors: Keating
authors: Steven G
authors: SG
authors: Deeks
authors: Peter W
authors: PW
authors: Hunt
authors: Jeffrey N
authors: JN
authors: Martin
authors: Michael G
authors: MG
authors: Rosenberg
authors: Frederick M
authors: FM
authors: Hecht
authors: Douglas F
authors: DF
authors: Nixon
mesh_terms: D000938:Antigen-Presenting Cells; D015703:Antigens, CD; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D039961:Semaphorins / Q000172:deficiency*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D016207:Cytokines; D039961:Semaphorins