Leishmania donovani: role of CD2 on CD4+ T-cell function in Visceral Leishmaniasis.
In this study, we investigated whether alteration in the CD2 mediated coordination of an immune response was associated with down regulation of CD4 associated Th1 cell response during Visceral Leishmaniasis (VL). Leishmania donovani (Ld) infection in VL patients markedly reduced expression of CD2 cell surface antigen on CD4+ cells. T-cells of VL patients were mostly in G0/G1 stage of the cell cycle (98.20%) with little or no activity of protein kinase C-alpha (PKC-alpha) isoform. However, pre-incubation with activating anti-CD2 monoclonal antibody (MAb) resulted in a corresponding increase up to 2.52-fold in T-cells of G2/M population supported by both activity and expression of PKC-alpha isoform. Furthermore, we observed that co-incubation of T-cell with anti-CD2 increased the lymphocyte-blast population in patients in whom the CD4 cells became more antigen responsive (CD4+ CD69+ cells). Consistent with these observations, it was shown that 59.3% of CD4 cells from patients responded to Ld by producing IFN-gamma. Even in the culture condition, when the T-cells from patients were depleted of APC, IFN-gamma production was noticed after CD2 activation. On the other hand, IL-4 production became low in the anti-CD2 antibody supplemented peripheral blood mononuclear cells (PBMNCs) culture. These findings imply that infection with L. donovani induces less CD2 on the surface of CD4+ T-cells, which once activated orchestrate the protective IFN-gamma dominant host defense mechanism via PKC-mediated signal transduction and cell cycle.
Bimal
Sanjiva
S
Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences (ICMR), Agamkuan, Patna 800007, India. drsbimal@yahoo.com
Singh
Shubhankar K
SK
Sinha
Sukrat
S
Pandey
Krishna
K
Sinha
Prabhat K
PK
Ranjan
Alok
A
Bhattacharya
Sujit K
SK
Das
Pradeep
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D018801:CD2 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051571:Protein Kinase C-alpha / Q000378:metabolism
D018801:CD2 Antigens; D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma; D051571:Protein Kinase C-alpha