| Full text | |
| 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 Opportunities: | Research Grants - Visiting Researcher Grant - International |