Infection of CD127+ (interleukin-7 receptor+) CD4+ cells and overexpression of CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human immunodeficiency virus type 1 infection
| Autor: | Mee Ling Munier, Pat Grey, David A. Cooper, John Zaunders, Daniel Kaufmann, Alan L. Landay, Barbara Fazekas de St Groth, Kersten K. Koelsch, Nabila Seddiki, Susanna Ip, John M. Kaldor, Eric S. Rosenberg, Anthony D. Kelleher, Robert Finlayson, Bruce D. Walker, Choechoe Brereton, Sarah C. Sasson, Kazuo Suzuki |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Receptors CCR5 Immunology HIV Infections Biology Microbiology Polymerase Chain Reaction T-Lymphocytes Regulatory Interleukin 21 Antigens CD T-Lymphocyte Subsets Virology Cytotoxic T cell Humans CTLA-4 Antigen IL-2 receptor Antigen-presenting cell Interleukin 3 Protein Tyrosine Phosphatase Non-Receptor Type 1 CD40 Receptors Interleukin-7 virus diseases hemic and immune systems Receptors Interleukin-2 Natural killer T cell Flow Cytometry Molecular biology ADP-ribosyl Cyclase 1 Antigens Differentiation Insect Science DNA Viral Interleukin 12 biology.protein HIV-1 Leukocyte Common Antigens Pathogenesis and Immunity |
| Zdroj: | Journal of virology. 80(20) |
| ISSN: | 0022-538X |
| Popis: | We recently found that human immunodeficiency virus (HIV)-specific CD4+T cells express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1 infection (PHI) but then rapidly disappear from the circulation. This cell loss may be due to susceptibility to infection with HIV-1 but could also be due to inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of the circulation, or dysfunction. We purified CD38+++CD4+T cells from peripheral blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that about 10% of this population was infected. However, a small subset of HIV-specific CD4+T cells also expressed CD127, a marker of long-term memory cells. Purified CD127+CD4+lymphocytes contained fivefold more copies of HIV-1 DNA per cell than did CD127-negative CD4+cells, suggesting preferential infection of long-term memory cells. We observed no apoptosis of antigen-specific CD4+T cells in vitro and only a small increase in CD45RO+CD25+CD127dimCD4+T regulatory cells during PHI. However, 40% of CCR5+CD38+++CD4+T cells expressed gut-homing integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT). Furthermore, 80% of HIV-specific CD4+T cells expressed high levels of the negative regulator CTLA-4 in response to antigen stimulation in vitro, which was probably contributing to their inability to produce interleukin-2 and proliferate. Taken together, the loss of HIV-specific CD4+T cells is associated with a combination of an infection of CCR5+CD127+memory CD4+T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4. |
| Databáze: | OpenAIRE |
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