Modulation of T cell responses in HTLV-1 carriers and in patients with myelopathy associated with HTLV-1.
OBJECTIVE
Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-gamma and TNF-alpha. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-gamma production was investigated.


METHODS
IFN-gamma levels were measured by ELISA before and after addition of cytokines or anti-cytokines.


RESULTS
Addition of IL-10 significantly reduced spontaneous IFN-gamma synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-gamma levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-beta. In paired analysis, neutralization of IL-2 significantly decreased IFN-gamma production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-gamma production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-gamma synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-gamma levels by 27%.


CONCLUSIONS
Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.
Santos
Silvane B
SB
Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Salvador, Brazil.
Porto
Aurélia F
AF
Muniz
André Luiz
AL
Luna
Tania
T
Nascimento
Márcia C
MC
Guerreiro
Jaqueline B
JB
Oliveira-Filho
Jamary
J
Morgan
Daniel J
DJ
Carvalho
Edgar M
EM
D000368:Aged; D002353:Carrier State / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D049669:History, 16th Century; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000378:metabolism; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D019409:Interleukin-15; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma