HIV-1 matrix protein p17 prevents loss of CD28 expression during IL-2-induced maturation of naïve CD8(+) T cells.
Naïve CD8(+) T cells differentiate into effectors secreting various cytokines that modulate immune functions. A striking finding for most HIV-1-infected patients is that they accumulate CD8(+) T cells belonging to early and intermediate differentiated elements. Structural HIV-1 proteins, and among these the matrix protein p17, have been associated with loss of functional competence by different immune cells. We therefore evaluated the influence of p17 on naïve CD8(+) T-cell activation and maturation. Anti-CD3 mAb preactivation and subsequent IL-2 stimulation are able to drive human naive CD(+) T cells to an effector phenotype characterized, among other features, by downregulation of the co-stimulatory molecule CD28. Strikingly, however, IL-2-induced downmodulation of CD28 was completely prevented by p17, and cells derived from p17-stimulated cultures showed a strong Tc1 polarization that was fourfold higher than that observed in IL-2-stimulated cultures.Moreover, p17 preserved a markedly high proportion of CD8(+) T cells that were able to respond to CD28 triggering with a proinflammatory cytokine storm. Our evidence suggests that p17 has important effects on cytokine polarization and phenotype of terminally differentiated CD8(+) T cells, and that new p17-based therapeutic approaches could control or prevent HIV-1-related immune disorders.
Department of Experimental and Applied Medicine, Section of Microbiology, University of Brescia Medical School, Brescia, Italy.
Manuela
M
Avolio
Sonia
S
Caracciolo
Giorgio
G
Tosti
Luana
L
Vollero
Simona
S
Fiorentini
Arnaldo
A
Caruso
D018106:CD28 Antigens / Q000096:biosynthesis*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; D015488:HIV Antigens; D007376:Interleukin-2; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1