Human CD4+ T-cell clone expansion leads to the expression of the cysteine peptidase inhibitor cystatin F

Milica Perišić (Author), Graham Pawelec (Author), Janko Kos (Author)

Abstract

The existence of CD4+ cytotoxic T cells (CTLs) at relatively high levels under different pathological conditions in vivo suggests their role in protective and/or pathogenic immune functions. CD4+ CTLs utilize the fundamental cytotoxic effector mechanisms also utilized by CD8+ CTLs and natural killer cells. During long-term cultivation, CD4+ T cells were also shown to acquire cytotoxic functions. In this study, CD4+ human T-cell clones derived from activated peripheral blood lymphocytes of healthy young adults were examined for the expression of cytotoxic machinery components. Cystatin F is a protein inhibitor of cysteine cathepsins, synthesized by CD8+ CTLs and natural killer cells. Cystatin F affects the cytotoxic efficacy of these cells by inhibiting the major progranzyme convertases cathepsins C and H as well as cathepsin L, which is involved in perforin activation. Here, we show that human CD4+ T-cell clones express the cysteine cathepsins that are involved in the activation of granzymes and perforin. CD4+ T-cell clones contained both the inactive, dimeric form as well as the active, monomeric form of cystatin F. As in CD8+ CTLs, cysteine cathepsins C and H were the major targets of cystatin F in CD4+ T-cell clones. Furthermore, CD4+ T-cell clones expressed the active forms of perforin and granzymes A and B. The levels of the cystatin F decreased with time in culture concomitantly with an increase in the activities of granzymes A and B. Therefore, our results suggest that cystatin F plays a role in regulating CD4+ T cell cytotoxicity. Since cystatin F can be secreted and taken up by bystander cells, our results suggest that CD4+ CTLs may also be involved in regulating immune responses through cystatin F secretion.

Keywords

cystatin F;CD4+ T helper cells;cytotoxic lymphocytes;peptidases;granzymes;

Data

Language:	English
Year of publishing:	2021
Typology:	1.01 - Original Scientific Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	577
COBISS:	72774659
ISSN:	1661-6596
Views:	97
Downloads:	45
Average score:	0 (0 votes)
Metadata:

Other data

Type (COBISS):	Article
Pages:	str. 8408-1-8408-15
Volume:	ǂVol. ǂ22
Issue:	ǂno. ǂ16
Chronology:	2021
DOI:	10.3390/ijms22168408
ID:	14889998