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

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]

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

• 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