CD8+ T Cells in HIV Disease Exhibit Cytokine Receptor Perturbation and Poor T Cell Receptor Activation but Are Responsive to γ-Chain Cytokine--Driven Proliferation

Pahwa, Rajendra; McCloskey, Thomas W.; Aroniadis, Olga C.; Strbo, Natasa; Krishnan, Subramaniam; Pahwa, Savita
March 2006
Journal of Infectious Diseases;3/15/2006, Vol. 193 Issue 6, p879
Academic Journal
Background. Cytokines are important for inducing T cell maturation, proliferation, and survival. Despite the known dysregulation of cytokines in human immunodeficiency virus (HIV) infection, cytokine receptor expression is relatively unexplored. Methods. We examined maturation markers (naive, central memory, effector memory, and effector); the cytokine receptors interleukin (IL)-2Rβ, common γ (Cγ) chain, IL-7Rα, IL-15Rα; and proliferative responses of T cells in a cohort of HIV-infected pediatric patients (median age, 14.82 years) receiving antiretroviral therapy, arbitrarily designated as immunologic responders (group I) and nonresponders (group II) on the basis of a CD4+ T cell count cutoff of 25%. Results. Patients had increased percentages of effector memory CD8+ T cells, in comparison with those in healthy control subjects, with reduced expression of IL-7Rα in the central memory and effector memory subsets and of the Cγ chain in all maturation subsets of CD8+ T cells. IL-7Rα+CD8+ T cell percentages were directly correlated with CD4+ T cell percentages. In immunologic nonresponders, anti-CD3+ or HIV Gag antigen-induced CD8+ T cell proliferation was impaired, but proliferation in response to the homeostatic cytokines IL-2 and IL- 15 was preserved. Conclusions. Cytokine receptor deficiencies may contribute to immune deficiency in HIV-infected patients, and γ-chain-utilizing cytokines may play an important role in vivo in maintaining the memory subsets of T cells in patients with CD4+ T cell deficiency.


Related Articles

  • Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope. Iversen, Astrid K. N.; Stewart-Jones, Guillaume; Learn, Gerald H.; Christie, Natasha; Sylvester-Hviid, Christina; Armitage, Andrew E.; Kaul, Rupert; Beattie, Tara; Lee, Jean K.; Yanping Li; Chotiyarnwong, Pojchong; Tao Dong; Xiaoning Xu; Luscher, Mark A.; MacDonald, Kelly; Ullum, Henrik; Klarlund-Pedersen, Bente; Skinhøj, Peter; Fugger, Lars; Buus, Søren // Nature Immunology;Feb2006, Vol. 7 Issue 2, p179 

    Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2–restricted CTL epitope...

  • Repertoire Development and the Control of Cytotoxic/Effector Function in Human γδ TCells. Urban, Elizabeth M.; Chapoval, Andrei I.; Pauza, C. David // Clinical & Developmental Immunology;2010, p1 

    T cells develop into two major populations distinguished by their T cell receptor (TCR) chains. Cells with the αβ TCR generally express CD4 or CD8 lineagemarkers andmostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternate γδ TCR in humans generally do not...

  • Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif. Seet, Bruce T; Berry, Donna M; Maltzman, Jonathan S; Shabason, Jacob; Raina, Monica; Koretzky, Gary A; McGlade, C Jane; Pawson, Tony // EMBO Journal;2/7/2007, Vol. 26 Issue 3, p678 

    The relationship between the binding affinity and specificity of modular interaction domains is potentially important in determining biological signaling responses. In signaling from the T-cell receptor (TCR), the Gads C-terminal SH3 domain binds a core RxxK sequence motif in the SLP-76...

  • Continuous T cell receptor signaling required for synapse maintenance and full effector potential. Huppa, Johannes B.; Gleimer, Michael; Sumen, Cenk; Davis, Mark M. // Nature Immunology;Aug2003, Vol. 4 Issue 8, p749 

    Although signals through the T cell receptor (TCR) are essential for the initiation of T helper cell activation, it is unclear what function such signals have during the prolonged T cell-antigen-presenting cell contact. Here we simultaneously tracked TCR-CD3 complex and phosphoinositide 3-kinase...

  • Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Erwei Song; Pengcheng Zhu; Sang-Kyung Lee; Chowdhury, Dipanjan; Kussman, Steven; Dykxhoorn, Derek M; Yi Feng; Palliser, Deborah; Weiner, David B; Shankar, Premlata; Marasco, Wayne A; Lieberman, Judy // Nature Biotechnology;Jun2005, Vol. 23 Issue 6, p709 

    Delivery of small interfering RNAs (siRNAs) into cells is a key obstacle to their therapeutic application. We designed a protamine-antibody fusion protein to deliver siRNA to HIV-infected or envelope-transfected cells. The fusion protein (F105-P) was designed with the protamine coding sequence...

  • T-Cell Receptor γδ Bearing Cells in Normal Human Skin. Bos, Jan D.; Teunissen, Marcel B. M.; Cairo, Irina; Krieg, Suze R.; Kapsenberg, Martien L.; Das, Pranab K.; Borst, Jannie // Journal of Investigative Dermatology;Jan1990, Vol. 94 Issue 1, p37 

    T-cell antigen receptors (TCR) are divided into common αβ and less common γδ types. In the murine skin, TCR γδ+ cells have been reported to form the great majority of epidermal T lymphocytes. We have examined the relative contribution of TCR αβ+ and TCR γδ+ cells to...

  • Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex. Myers, Margaret D.; Sosinowski, Tomasz; Dragone, Leonard L.; White, Carmen; Band, Hamid; Gu, Hua; Weiss, Arthur // Nature Immunology;Jan2006, Vol. 7 Issue 1, p57 

    The adaptor molecule SLAP and E3 ubiquitin ligase c-Cbl each regulate expression of T cell receptor (TCR)–CD3 on thymocytes. Here we provide genetic and biochemical evidence that both molecules function in the same pathway. TCR-CD3 expression was similar in the absence of SLAP and/or...

  • Non-canonical NF-κB signaling pathway. Shao-Cong Sun // Cell Research;Jan2011, Vol. 21 Issue 1, p71 

    The non-canonical NF-κB pathway is an important arm of NF-κB signaling that predominantly targets activation of the p52/RelB NF-κB complex. This pathway depends on the inducible processing of p100, a molecule functioning as both the precursor of p52 and a RelB-specific inhibitor. A...

  • Normal T Cell Selection Occurs in CD205-Deficient Thymic Microenvironments. Jenkinson, William E.; Nakamura, Kyoko; White, Andrea J.; Jenkinson, Eric J.; Anderson, Graham // PLoS ONE;Dec2012, Vol. 7 Issue 12, p1 

    The thymus imparts a developmental imprint upon T cells, screening beneficial and self-tolerant T cell receptor (TCR) specificities. Cortical thymic epithelial cells (CTEC) present self-peptide self-MHC complexes to thymocytes, positively selecting those with functional TCRs. Importantly, CTEC...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics