We read the article by Mattarollo et al. (1) with great interest. They identified that CD1d-recruited invariant NKT (iNKT) cells had the ability to suppress immune effector mechanisms after specific attraction to persistent HPV16-E7–expressing hyperplastic lesions in a murine model.

Several studies have demonstrated the pivotal anti-tumor effect of iNKT cells in peripheral blood, but few of them refer to the local immune environment. We conducted a comprehensive literature search in PubMed for related articles, and finally found one that is available now. Miura et al. (2) reported 45 clinical cervical specimens in which CD1d was mostly limited to the human papillomavirus (HPV)-negative samples rather than HPV-positive ones. They hypothesized that the decreased CD1d expression mediated by HPV E5 inhibited the activation of iNKT cells, which may help HPV-infected cervical epithelia evade protective immune surveillance.

Although the activation of iNKT cells only depends on the recognition of CD1d, it is unclear whether the expression of CD1d definitely results in the activation of iNKT cells (3). In addition, the results of the murine model could not be analogized to humans directly. In humans, iNKT cells are characterized by the expression of a restricted αβ TCR (Vα24-Jα18 chain paired with Vβ11) (4). Therefore, it seems reasonable to detect iNKT cells by these specific Abs. In this way, we might find a clue to clarify the function of iNKT cells in human HPV-infected cervical epithelia, which is also a part of our current studies.

1
Mattarollo
S. R.
,
Rahimpour
A.
,
Choyce
A.
.
2010
.
Invariant NKT cells in hyperplastic skin induced a local immune suppressive environment by IFN-γ production.
J. Immunol.
184
:
1242
1250
.
2
Miura
S.
,
Kawana
K.
,
Schust
D. J.
.
2010
.
CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein: a possible mechanism for immune evasion by HPV.
J. Virol.
84
:
11614
11623
.
3
Brutkiewicz
R. R.
2006
.
CD1d ligands: the good, the bad and the ugly.
J. Immunol.
177
:
769
775
.
4
Bah
J. F.
,
Bendelac
A.
,
Brenner
M. B.
.
2004
.
The role of innate immunity in autoimmunity.
J. Exp. Med.
200
:
1527
1531
.