Modulation of T-Cell Responses to a Recall Antigen in Human T-Cell Leukemia Virus Type 1-Infected Individuals

Abstract

To determine the mechanism of the purified protein derivative (PPD)-specific hyporesponsiveness in Mycobacterium bovisBCG-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-γ) production in NP and PP (P < 0.02), with minimal proliferation and IFN-γ 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-γ in both nonresponder groups (NN and PN), suggesting that the lack of IFN-γ 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.

Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

“…However no information regarding microbiological, radiological or clinical data were provided to determine how HTLV-1 can exacerbate the clinical course of tuberculosis. As previous studies have shown that subjects infected with HTLV-1 have a decreased immune response “ in vivo ” and “in vitro” to PPD [ 17 - 19 , 21 ], one possibility is that HTLV-1, by decreasing the immune response to M. tuberculosis, not only increases susceptibility but also makes tuberculosis more severe. The results presented here did not show any difference in the frequency of patients who respond to the TST as well as in the size of the induration when the two groups were compared.…”

“…In vitro studies showed decrease in lymphocyte proliferation and secretion of cytokines upon stimulation with M. tuberculosis antigen in HTLV-1 infected subjects compared to controls [ 19 , 21 ]. Similar to the in vivo observations, the in vitro studies were also performed in HTLV-1 infected patients without history of tuberculosis.…”

“…Similar to the in vivo observations, the in vitro studies were also performed in HTLV-1 infected patients without history of tuberculosis. However, it is known that abnormalities in T cell or in antigen present cell function occur in HTLV-1 infection [ 21 - 23 ]. Therefore impairment in the Th1 type of immune response to mycobacterial antigens may increase susceptibility to tuberculosis.…”

Integrated miRNA and mRNA Expression Profiling to Identify mRNA Targets of Dysregulated miRNAs in Pulmonary Tuberculosis

“…Protective immunity to M. tuberculosis depends on correct function of T cells and their interaction with macrophages. HTLV-1 preferentially infects T cells and causes chronic T-cell dysfunction, which appears to impair the immune response to specific pathogens [ 30 ]. HTLV-1 infection may increase an individual's susceptibility to active TB [ 31 ].…”

HTLV-1 infection is associated with a history of active tuberculosis among family members of HTLV-1-infected patients in Peru

“…Protective immunity to M. tuberculosis depends on the correct function of T cells and their interaction with macrophages. HTLV-1 preferentially infects T cells and causes chronic T-cell dysfunction, which appears to result in an impaired immune response to specific pathogens [21]. Even though the mechanism and the impact of such immune suppression remain unknown, it makes an association between HTLV-1 and TB biologically plausible.…”