Impaired expression of CD26 compromises T-cell recruitment in human visceral leishmaniasis.
An inefficient Th1 response, coupled with skewed Th2 cytokine production, has been implicated to increase susceptibility to visceral leishmaniasis (VL) infection. The expression of the dipeptidyl peptidase Cd26 by polarized Th1 activates a chemokine cascade that recruits Th1 recruitment to the pathologic site. Here, we studied 42 patients with confirmed VL (mean age 24.80 ± 16.26 years; range 3-70 years; 25 males and 17 females), 30 endemic controls, and 10 nonendemic controls. We observed a decrease in constitutive and antigen-induced expression of CD26 on the T cells of VL patients. Soluble CD26 (sCD26) levels in serum and BM were also found to be significantly lower in VL patients. Following successful therapy, increased sCD26 expression was observed. Tuberculosis pleural effusion derived CCR5(+) CXCR3(+)  effector T cells showed enhanced chemokine-driven migration in the presence of posttreatment BM aspirate containing high levels of sCD26. Moreover, T-cell migration could be inhibited by blocking RANTES, IP-10, and CD26 signaling from the posttreatment aspirate with Ab. Our results indicate that, in VL patients, impaired expression and secretion of CD26 compromises chemokine activation and thus T-cell recruitment, eventually resulting in a deficient state of local immunity at pathologic sites.
Department of Transplant Immunology & Immunogenetics, AIIMS, New Delhi, India.
Ambak K
AK
Rai
Chandreshwar P
CP
Thakur
Prabin
P
Kumar
Dipendra K
DK
Mitra
D000293:Adolescent; D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking / Q000494:pharmacology; D002465:Cell Movement; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007165:Immunosuppression Therapy; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
D019138:Antibodies, Blocking; D016207:Cytokines; D018819:Dipeptidyl Peptidase 4