Table 1.

Key findings describing changes in the CD4⁺ T cell compartment of patients with pSS

Finding	Reference
Blood
CD4+ T cell lymphopenia is a predictive factor of lymphoma development and is associated with higher systemic disease activity and with increased numbers of lymphocytes in MSGs of pSS patients.	[17, 18, 85]
Different subtypes of IL-17-producing CD4+ T cells are enriched in peripheral blood from at least a subgroup of pSS patients.	[3, 23, 38, 42]
Frequencies of memory Treg cells are increased in peripheral blood from pSS patients, at least in patients with moderate–high disease activity.	[3, 51, 52]
Frequencies of circulating Tfh cells are increased in pSS patients compared with non-SS sicca controls and healthy individuals. Frequencies of activated cTfh cells (CD4+CD45RA−CXCR5+PD-1+ICOS+) correlate with systemic disease activity.	[3, 23, 62, 63]
Circulating Tfr cells are enriched in peripheral blood from pSS patients, resulting in a higher cTfr:cTfh ratio in pSS patients compared with healthy individuals.	[62, 63]
The proportion of CCR9+ ‘Tfh-like’ cells is increased in peripheral blood from pSS patients compared with healthy individuals.	[75]
Tissue
IFN-γ-producing CD4+ T cells (Th1 cells) are present within lymphocytic infiltrates and IFN-γ (type II IFN) activity is associated with the degree of CD45+ infiltration in MSGs of pSS patients.	[21, 24]
IL-17 protein and mRNA is increased in MSG tissue of pSS patients compared with non-SS sicca controls.	[35–37]
The frequency of FoxP3+ cells in MSGs correlates positively with the biopsy focus score.	[37, 53]
Tfh-like cells (CD4+PD-1+ICOS+) make up a significant part of the T cell infiltrate in MSGs of pSS patients and likely form a major source of IL-21.	[63]
The TCR repertoire of glandular CD4+ T cells indicates local antigen recognition (and expansion) by these cells.	[79]