Gamma/Delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections.
The objective of this study was to functionally assess gamma/delta (gammadelta) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. gammadelta T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4(+) T cells/mul blood) or CD4-low (<200 CD4 cells/mul blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the Vdelta2 gammadelta T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of gammadelta T cells in their peripheral blood than humans did. Following stimulation, gammadelta T cells from SIV-positive (SIV(+)) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4(+) T-cell levels. In contrast, HIV-positive (HIV(+)) patients exhibited a decreased percentage of gammadelta T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the Vdelta2(+) gammadelta T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their gammadelta T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV(+) patients. The SIV(+) sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that gammadelta T-cell dysfunction occurs in HIV(+) patients and may contribute to HIV disease progression.
Kosub
David A
DA
Seattle Biomedical Research Institute, 307 Westlake Ave. N., Seattle, WA 98109, USA.
Lehrman
Ginger
G
Milush
Jeffrey M
JM
Zhou
Dejiang
D
Chacko
Elizabeth
E
Leone
Amanda
A
Gordon
Shari
S
Silvestri
Guido
G
Else
James G
JG
Keiser
Philip
P
Jain
Mamta K
MK
Sodora
Donald L
DL
D000328:Adult; D000818:Animals; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D016665:Cercocebus atys; D005434:Flow Cytometry; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016180:Lentivirus Infections / Q000276:immunology*; D008875:Middle Aged; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma