Sl. No. Clinical Condition Finding Reference
1. Rheumatoid Arthritis (RA) Polymorphisms in FOXP3 gene associated with reduced frequency of Treg, TGFβ and IL-10, in RA [29]
Increased circulating HLA-DR+Tregs or inflammation-associated Tregs which are suppressive but have similar TCR repertoire as pathogenic CD4+ T cells [30]
Reduced frequencies of nTreg in patients with RA [31]
Tregs unable to suppress spontaneous generation of TNFα in synovial cells of RA patients due to reduced expression of CTLA-4 and LFA-1 [32]
2. Multiple Sclerosis (MS) CD4+CD25+ Treg cells/Treg-derived exosomes from multiple sclerosis patients are inefficiently suppressive. Circulating exosomes with significantly high miRNA let-7i in MS patients, inhibit Treg function through an IGFR1 and TGFBR1 mechanism. [33-35]
CD25+CD127low Treg development and function are perturbed. CD39+FoxP3+ memory Treg are diminished in MS patients. Expression of PD-1 is high on theses Tregs in MS, suggesting possible exhaustion and compromised function. [36,37]
3. Systemic Lupus Erythromatosis (SLE) CD25+Lag3+ T cells, expressing FoxP3 and IL-17A, but not being suppressive are increased in patients with SLE. The frequency of CD25+Lag3+ cells positively correlates with SLE disease activity. [38]
4. Type 1 Diabetes Reduced suppressive function of Treg cells in Type 1 diabetes patients possibly due to reduced CD39 expression on memory Treg cells. [39]
Differentiation and stability of Tregs is impaired in Type 1 diabetes through a miRNA-1423p dependent mechanism. [40]
FoxP3 expression declines with type 1 diabetes disease progression suggesting loss in Treg function. The rate of loss is greatest in Peptidase inhibitor -16 or Pi16+ Treg cells [41]
5. Malaria FoxP3+Treg cells increase in humans and mice during blood stage malaria and hamper Th and Tfh-B cell interactions. [42]
Frequency of FoxP3+ Tregs declines in children with age in high exposure malaria settings. [43]
6. Dengue Treg frequencies are higher in mild cases of dengue compared to moderate cases and healthy controls. [44]
Treg frequencies in acute dengue fever are high and most of the expanded Treg population comprises of naïve Tregs with poor suppressive potential. [45]
7. HIV HIV infected paediatric slow progressors have higher Treg absolute numbers with a suppressive phenotype compared to rapid progressors. [46]
Depletion of CD4+CD25hiCD62Lhi Tregs are depleted in HIV infection and this correlates with immune activation. [47]
HIV+ elite suppressors maintain higher levels of Treg and lower immune activation compared to progressors. [48]
Frequency of PD-1+ Tregs increases in HIV and blockade of the PD-1/PD-L1 pathway increases TGF-β and IL-10 in CD4+CD25hiCD127loTreg cells. [49]
Individuals who do not respond to ART have fewer dysfunctional Tregs with defects in mitochondrial function compared to healthy controls and HIV patients who respond to ART. [50]
8. Candida infection Candida albicans infection in a mouse model drives expansion of Tregs which corresponds with increased fungal burden. Expanded Tregs suppress Th1 and Th2 but promote pathogenic Th17 responses. [51, 52]
9.
Leishmaniasis
Foxp3+IL-10+ Treg cells are enriched in bone marrow of visceral leishmaniasis patients with high parasite load compared to those with low parasite load. Frequency of CD4+CD25hiFoxP3+ Treg cells correlates with parasite load in Kala-azar patients infected with Leishmania donovani.
[53, 54]
10. Tuberculosis While some studies have found Treg frequencies to increase in blood and lungs of TB patients, others have found them to remain unchanged. [55-61]