Expression of CD8α identifies a distinct subset of effector memory CD4⁺ T lymphocytes

Abstract

Summary Circulating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8αα homodimer, while the minor population was CD4lo CD8hi and expressed the CD8αβ heterodimer. The majority of CD4hi CD8αlo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7– CD28– HLA‐DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus‐specific T cells was enriched five‐fold in CD4hi CD8αlo T cells compared to single‐positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)‐specific T cells. Cross‐sectional studies of SIV‐infected animals demonstrated that the frequency of CD4hi CD8αlo T cells was lower in wild‐type SIV‐infected animals compared to uninfected controls, although prospective studies of SIV‐infected animals demonstrated depletion of CD4hi CD8αlo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8α represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection.

Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection

“…Surface staining was carried out by standard procedures for our laboratory as described [56]. Except where noted, all reagents were obtained from BD Biosciences (San Diego, CA) and included monoclonal antibodies to the following molecules: CD3 (clone SP34-2, APC-Cy7 conjugate) CD4 (clone SK3, PerCP-Cy5.5 conjugate), CD8α (clone RPA-T8, Alexa700 conjugate) CD28 (clone CD28.2, PE-Texas Red conjugate, Beckman-Coulter, Fullerton, CA), CCR7 (clone 150503, Pacific Blue conjugate, custom) CXCR3 (clone 1C6, PE-Cy5 conjugate), Ki-67 (Clone B56, PE conjugate), CD127 (clone R34.34, PE conjugate, Beckman-Coulter), perforin (clone Pf-344, FITC conjugate, Mabtech, Mariemont, OH).…”

Lsr2 of Mycobacterium leprae and Its Synthetic Peptides Elicit Restitution of T Cell Responses in Erythema Nodosum Leprosum and Reversal Reactions in Patients with Lepromatous Leprosy

“…The characteristic immunoreactive T cells associated with transient and limited proliferative responses with high levels of IFN-␥ production and cytotoxic function have been linked to a subset of effector memory (T EM ) cells in antigen-primed individuals (32)(33)(34). Repetitive antigen exposure is known to activate T EM cells.…”

CD4+/CD8+ double-positive T cells: more than just a developmental stage?

“…Whereas several studies support mature CD4 + T cells as the source of CD4/CD8 DP T cells [1,[41][42][43][44], evidence for CD8 as the lineage of origin for CD4/CD8 DP T cells also exists. For example, expression of CD4 on CD8 + T cells occurs following in vitro activation of human PBMCs [45], subsequently rendering them susceptible to HIV infection [46,47].…”