Abstract
Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), which can down-regulate T cell antigen receptor- mediated T cell function, including cytolytic activity. In the present study, we demonstrate that CD3+NKR+ cells can be identified in HIV-infected patients. HIV-specific cytolytic activity was analyzed in five patients in whom autologous lymphoblastoid B cell lines could be derived as a source of autologous target cells. Phytohemagglutinin-activated T cell populations that had been cultured in interleukin 2 displayed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env, gag, pol, and Nef in 3 of 5 patients. Addition of anti-NKR mAb of IgM isotype could increase the specific CTL activity. Moreover, in one additional patient, HIV-specific CTL activity was undetectable; however, after addition of anti-NKR mAb such CTL activity appeared de novo. Similar results were obtained by analysis of CD3+NKR+ clones derived from two patients. These data provide direct evidence that CD3+NKR+ cells may include antigen (HIV)-specific CTLs and that mAb- mediated masking of inhibitory NKR may revert the down-regulation of CTL function.
| Original language | English |
|---|---|
| Pages (from-to) | 10285-10288 |
| Number of pages | 4 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 94 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 1997 |
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ASJC Scopus subject areas
- Genetics
- General
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Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes : Impairment of specific cytolytic functions. / De Maria, A.; Ferraris, A.; Guastella, M.; Pilia, S.; Cantoni, C.; Polero, L.; Mingari, M. C.; Bassetti, D.; Fauci, A. S.; Moretta, L.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 19, 1997, p. 10285-10288.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes
T2 - Impairment of specific cytolytic functions
AU - De Maria, A.
AU - Ferraris, A.
AU - Guastella, M.
AU - Pilia, S.
AU - Cantoni, C.
AU - Polero, L.
AU - Mingari, M. C.
AU - Bassetti, D.
AU - Fauci, A. S.
AU - Moretta, L.
PY - 1997
Y1 - 1997
N2 - Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), which can down-regulate T cell antigen receptor- mediated T cell function, including cytolytic activity. In the present study, we demonstrate that CD3+NKR+ cells can be identified in HIV-infected patients. HIV-specific cytolytic activity was analyzed in five patients in whom autologous lymphoblastoid B cell lines could be derived as a source of autologous target cells. Phytohemagglutinin-activated T cell populations that had been cultured in interleukin 2 displayed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env, gag, pol, and Nef in 3 of 5 patients. Addition of anti-NKR mAb of IgM isotype could increase the specific CTL activity. Moreover, in one additional patient, HIV-specific CTL activity was undetectable; however, after addition of anti-NKR mAb such CTL activity appeared de novo. Similar results were obtained by analysis of CD3+NKR+ clones derived from two patients. These data provide direct evidence that CD3+NKR+ cells may include antigen (HIV)-specific CTLs and that mAb- mediated masking of inhibitory NKR may revert the down-regulation of CTL function.
AB - Human T lymphocytes have been shown to express inhibitory natural killer cell receptors (NKR), which can down-regulate T cell antigen receptor- mediated T cell function, including cytolytic activity. In the present study, we demonstrate that CD3+NKR+ cells can be identified in HIV-infected patients. HIV-specific cytolytic activity was analyzed in five patients in whom autologous lymphoblastoid B cell lines could be derived as a source of autologous target cells. Phytohemagglutinin-activated T cell populations that had been cultured in interleukin 2 displayed HIV-specific cytotoxic T lymphocyte (CTL) activity against HIV env, gag, pol, and Nef in 3 of 5 patients. Addition of anti-NKR mAb of IgM isotype could increase the specific CTL activity. Moreover, in one additional patient, HIV-specific CTL activity was undetectable; however, after addition of anti-NKR mAb such CTL activity appeared de novo. Similar results were obtained by analysis of CD3+NKR+ clones derived from two patients. These data provide direct evidence that CD3+NKR+ cells may include antigen (HIV)-specific CTLs and that mAb- mediated masking of inhibitory NKR may revert the down-regulation of CTL function.
UR - http://www.scopus.com/inward/record.url?scp=0030922880&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030922880&partnerID=8YFLogxK
U2 - 10.1073/pnas.94.19.10285
DO - 10.1073/pnas.94.19.10285
M3 - Article
C2 - 9294202
AN - SCOPUS:0030922880
VL - 94
SP - 10285
EP - 10288
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 19
ER -