{"id":21265,"date":"2013-04-01T11:50:40","date_gmt":"2013-04-01T11:50:40","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=21265"},"modified":"2013-04-03T09:42:33","modified_gmt":"2013-04-03T09:42:33","slug":"cd4-t-cells-specific-for-different-pathogens-vary-in-susceptibility-to-hiv-infection","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/21265","title":{"rendered":"CD4 T cells specific for different pathogens vary in susceptibility to HIV infection"},"content":{"rendered":"

Richard Jefferys, TAG<\/strong><\/p>\n

When it comes to susceptibility to HIV infection, not all CD4 T cells are created equal.<\/strong><\/p>\n

There are a variety of factors that have been shown to influence how readily HIV gains entry and replicates, with the best-described distinction being between activated CD4 T cells, which are highly susceptible, and resting CD4 T cells, which are relatively resistant. The particular types of cytokines and chemokines that a CD4 T-cell makes have also been shown to influence the efficiency of HIV infection.<\/p>\n

Less well understood is the influence of antigen specificity – the pathogen being targeted by the CD4 T cell. Evidence has been published showing that TB-specific CD4 T cells are highly susceptible [1], whereas those responding to the viral infection CMV are relatively resistant [2] (with this resistance being associated with the release of beta-chemokines capable of binding the CCR5 receptor and blocking HIV entry). A study by Haitao Hu and colleagues from the US Military HIV Research Program has now explored this issue further by looking at the susceptibility of various pathogen-specific CD4 T cells and the relationship with the genes that the different cells express. [3]<\/p>\n

The results confirm that CMV-specific CD4 T cells are highly resistant to HIV, but not just due to release of beta-chemokines: gene expression analyses revealed that the cells also upregulate several innate antiviral factors such as IFIT1 (a protein that recognises a particular form of viral RNA). Because of these factors, CMV-specific CD4 T cells displayed reduced susceptibility to HIV infection even when the researchers used antibodies to neutralise any effect of beta-chemokines. In contrast, CD4 T cells specific for Tetanus Toxoid (TT) and Candida exhibited a pro-inflammatory Th17-type profile and were highly permissive to HIV infection. The researchers suggest that these differences in susceptibility may contribute to the well-documented relationship between differing levels of immune deficiency and risk of specific opportunistic infections; i.e. candidiasis is typically an early sign of immune deficiency whereas active CMV disease almost exclusively occurs at extremely low CD4 T cell levels.<\/p>\n

Another important implication of the study is that HIV vaccines should aim to induce HIV-specific CD4 T cells with a profile that resembles CMV-specific responses. The researchers speculate that there may be a connection between their observations and the fact that the best results obtained to date in the stringent SIV\/macaque model of vaccination have involved a CMV-based vaccine vector. [4]<\/p>\n

Several research groups – including those of Louis Picker at the Oregon Health & Science University and Rafick-Pierre Sekaly at the Vaccine & Gene Therapy Institute in Florida – are now working to develop CMV-based HIV vaccine vectors with the aim of conducting human studies in both the therapeutic and preventive contexts.<\/p>\n

Source:<\/p>\n

TAG Web Blog. CD4 T cells specific for different pathogens vary in susceptibility to HIV infection. TAG web Blog. (6 February 2013).<\/p>\n

http:\/\/tagbasicscienceproject.typepad.com\/<\/a><\/p>\n

References:<\/p>\n

    \n
  1. Geldmacher C et al. Preferential infection and depletion of Mycobacterium tuberculosis\u2013specific CD4 T cells after HIV-1 infection. J Exp Med. 2010, December 20; 207(13): 2869\u20132881. doi: 10.1084\/jem.20100090.
    \n    http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3005236\/<\/a><\/li>\n
  2. Casazza JP et al. Autocrine production of Beta-chemokines protects CMV-specific CD4+ T cells from HIV infection. PLoS Pathog. 30 October 2009; 5(10): e1000646. doi: 10.1371\/journal.ppat.1000646.
    \n    http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2763204<\/a><\/li>\n
  3. Hu H et al. Distinct gene expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection. Blood, Early online 20 December 2012, doi: 10.1182\/blood-2012-07-446278.
    \n    http:\/\/bloodjournal.hematologylibrary.org\/content\/early\/2012\/12\/19\/blood-2012-07-446278.abstract<\/a><\/li>\n
  4. Hansen SG. Profound early control of highly pathogenic SIV by an effector-memory T cell vaccine. Nature. 2011 May 26; 473(7348): 523\u2013527. Published online 2011 May 11. doi: 10.1038\/nature10003.
    \n    http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3102768\/<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Richard Jefferys, TAG When it comes to susceptibility to HIV infection, not all CD4 T cells are created equal. There are a variety of factors that have been shown to influence how readily HIV gains entry and replicates, with the …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[15],"tags":[],"class_list":["post-21265","post","type-post","status-publish","format-standard","hentry","category-basic-science-and-immunology"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/21265","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=21265"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/21265\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=21265"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=21265"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=21265"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}