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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The CD8(+) Memory Stem T Cell (T-SCM) Subset Is Associated with Improved Prognosis in Chronic HIV-1 Infection

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Author(s):
Ribeiro, Susan P. [1, 2] ; Milush, Jeffrey M. [3] ; Cunha-Neto, Edecio [1, 2, 4] ; Kallas, Esper G. [1, 2] ; Kalil, Jorge [1, 5, 2, 4] ; Somsouk, Ma [6] ; Hunt, Peter W. [7] ; Deeks, Steven G. [7] ; Nixon, Douglas F. [8] ; SenGupta, Devi [3]
Total Authors: 10
Affiliation:
[1] INCT, Inst Invest Immunol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, LIM60, Lab Clin Immunol & Allergy, Sao Paulo - Brazil
[3] Univ Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA 94143 - USA
[4] Univ Sao Paulo, Sch Med, Inst Heart, Immunol Lab, Sao Paulo - Brazil
[5] Butantan Inst, Sao Paulo - Brazil
[6] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA 94143 - USA
[7] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div HIV AIDS, San Francisco, CA 94143 - USA
[8] George Washington Univ, Dept microbiol Immunol & Trop Med, Washington, DC - USA
Total Affiliations: 8
Document type: Journal article
Source: Journal of Virology; v. 88, n. 23, p. 13836-13844, DEC 2014.
Web of Science Citations: 15
Abstract

Memory stem T cells (T-SCM) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. The hallmarks of HIV-1 pathogenesis are CD4(+) T cell depletion and abnormal cellular activation. We investigated the impact of HIV-1 infection on the T-SCM compartment, as well as any protective role these cells may have in disease progression, by characterizing this subset in a cohort of 113 subjects with various degrees of viral control on and off highly active antiretroviral therapy (HAART). We observed that the frequency of CD8(+) T-SCM was decreased in all individuals with chronic, untreated HIV-1 infection and that HAART had a restorative effect on this subset. In contrast, natural controllers of HIV-1 had the highest absolute number of CD4(+) T-SCM cells among all of the infected groups. The frequency of CD4(+) T-SCM predicted higher CD8(+) T-SCM frequencies, consistent with a role for the CD4(+) subset in helping to maintain CD8(+) memory T cells. In addition, T-SCM appeared to be progenitors for effector T cells (TEM), as these two compartments were inversely correlated. Increased frequencies of CD8(+) T-SCM predicted lower viral loads, higher CD4(+) counts, and less CD8(+) T cell activation. Finally, we found that T-SCM express the mucosal homing integrin alpha(4)beta(7) and can be identified in gut-associated lymphoid tissue (GALT). The frequency of mucosal CD4(+) T-SCM was inversely correlated with that in the blood, potentially reflecting the ability of these self-renewing cells to migrate to a crucial site of ongoing viral replication and CD4(+) T cell depletion. IMPORTANCE HIV-1 infection leads to profound impairment of the immune system. T-SCM constitute a recently identified lymphocyte subset with stem cell-like qualities, including the ability to generate other memory T cell subtypes, and are therefore likely to play an important role in controlling viral infection. We investigated the relationship between the size of the CD8(+) T-SCM compartment and HIV-1 disease progression in a cohort of chronically infected individuals. Our results suggest that HAART restores a normal frequency of CD8(+) T-SCM and that the natural preservation of this subset in the setting of untreated HIV-1 infection is associated with improved viral control and immunity. Therefore, the CD8(+) T-SCM population may represent a correlate of protection in chronic HIV-1 infection that is directly relevant to the design of T cell-based vaccines, adoptive immunotherapy approaches, or the pharmacologic induction of T-SCM. (AU)

FAPESP's process: 10/05845-0 - Cellular immune responses in infectious diseases and primary immunodeficiencies
Grantee:Esper Georges Kallás
Support type: Research Grants - Visiting Researcher Grant - International