The chronic chikungunya arthritis symptoms closely mimic the rheumatoid arthritis (RA) symptoms, thus making it difficult to distinguish between these two clinical entities. The current comparative study characterizes NK (CD3(-)CD56(+)) and NK-like T (CD3(+)CD56(+)) cell responses in patients with chronic chikungunya arthritis and RA. Phenotype and functions of NK and NK-like T cells repertoire were assessed in 56 chronic chikungunya arthritis, 26 RA patients and 82 controls using flow cytometry. TNF-alpha and IFN-gamma-secreting NK-like T cells were high in both chronic arthritis patients than in controls. Percentage of TNF-alpha(+) NK cells was higher in RA patients than in controls. Percentage of perforin(+) NK cells was low in both chronic arthritis patient groups. Among the patient groups, expressions of perforin(+) and IFN-gamma(+) NK-like T cells were higher in RA. Overall, our data show reduced frequency of NK-like T cells, lower expression of perforin* NK, higher expression of TNF-alpha NK-like T and IFN-gamma(+) NK-like T cells as the markers of chronic arthritic diseases. In the absence of any specific treatment for chronic chikungunya induced arthritis and promising results of anti-TNF-alpha therapy against RA, current data may form the basis for future in vivo studies and has scope as possible therapeutics against chikungunya. (C) 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.