Modulation of T-cell responses to a recall antigen in human T-cell leukemia virus type 1-infected individuals.
To determine the mechanism of the purified protein derivative (PPD)-specific hyporesponsiveness in Mycobacterium bovis BCG-vaccinated human T-cell leukemia virus type 1 (HTLV-1)-infected individuals, we examined cytokine production in response to PPD in the following four groups of individuals: (i) HTLV-negative, PPD nonresponders (n = 11; NN); (ii) HTLV-negative, PPD responders (n = 18; NP); (iii) HTLV-positive, PPD nonresponders (n = 15; PN); and (iv) HTLV-positive, PPD responders (n = 15; PP). In vitro stimulation with PPD resulted in both proliferative responses and gamma interferon (IFN-gamma) production in NP and PP (P < 0.02), with minimal proliferation and IFN-gamma production in the NN and PN groups. Further, PPD-specific interleukin 10 (IL-10) production was significantly reduced in the PN group (P < 0.01), while the other groups had comparable levels. Cytokine reconstitution experiments demonstrated that while addition of recombinant IL-12 (rIL-12) plus anti-IL-4 restored PPD-specific responses in the NN group, it had no effect in the PN group. However, addition of rIL-12 resulted in the increased production of IFN-gamma in both nonresponder groups (NN and PN), suggesting that the lack of IFN-gamma production was not responsible for the PPD anergy. We conclude that PPD-specific anergy in HTLV-1-infected individuals appears to be due in part to their inability to respond to rIL-12.
Suzuki
M
M
Retrovirus Disease Branch, Division of AIDS, STD, and TB Laboratory Research, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Dezzutti
C S
CS
Okayama
A
A
Tachibana
N
N
Tsubouchi
H
H
Mueller
N
N
Lal
R B
RB
D000942:Antigens, Bacterial / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D009163:Mycobacterium bovis / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium; D014373:Tuberculin / Q000276:immunology*
D000942:Antigens, Bacterial; D000956:Antigens, Viral; D001500:BCG Vaccine; D007376:Interleukin-2; D011994:Recombinant Proteins; D014373:Tuberculin; D014316:Tritium; D018664:Interleukin-12; D007371:Interferon-gamma; D013936:Thymidine